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Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-07-2103.
IMMUNOBIOLOGY
From the Vaccine Research Center and the Laboratory of
Immunoregulation, National Institute of Allergy and Infectious Diseases
(NIAID), National Institutes of Health (NIH), and the Experimental
Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the
Departments of Pathology and Neurology, University of Texas,
Southwestern Medical Center, Dallas.
Virus-specific CD8+ T-cell responses play a pivotal
role in limiting viral replication. Alterations in these responses,
such as decreased cytolytic function, inappropriate maturation, and limited proliferative ability could reduce their ability to control viral replication. Here, we report on the capacity of HIV-specific CD8+ T cells to secrete cytokines and proliferate in
response to HIV antigen stimulation. We find that a large proportion of
HIV-specific CD8+ T cells that produce cytokines in
response to cognate antigen are unable to divide and die during a
48-hour in vitro culture. This lack of proliferative ability of
HIV-specific CD8+ T cells is defined by surface expression
of CD57 but not by absence of CD28 or CCR7. This inability to
proliferate in response to antigen cannot be overcome by exogenous
interleukin-2 (IL-2) or IL-15. Furthermore, CD57 expression on
CD8+ T cells, CD4+ T cells, and NK cells is a
general marker of proliferative inability, a history of more cell
divisions, and short telomeres. We suggest, therefore, that the
increase in CD57+ HIV-specific CD8+ T cells
results from chronic antigen stimulation that is a hallmark of HIV
infection. Thus, our studies define a phenotype associated with
replicative senescence in HIV-specific CD8+ T cells,
which may have broad implications to other conditions associated with
chronic antigenic stimulation.
(Blood. 2003;101:2711-2720) CD8+ T cells are crucial to the
recognition and clearance of virus-infected cells.1,2
Fully functional CD8+ T cells have the ability to
proliferate and mediate antiviral activity through cytokine and
chemokine secretion, Fas/Fas ligand interactions, and/or
perforin/granzyme-mediated cell lysis after recognition of cognate
antigen. When naive CD8+ T cells are activated during a
primary viral infection, they proliferate and become effector T cells
that fulfill these functions.2,3 Following clearance of
virus, the majority of the virus-specific CD8+ T cells die,
and few memory CD8+ T cells remain to combat subsequent
infections with further rounds of proliferation and elaboration of
effector functions.
Studies have suggested that chronic stimulation of T cells, such
as that which occurs with rheumatoid arthritis,4-6
multiple myeloma,7 cytomegalovirus (CMV) and HIV
infections,8,9 and following bone marrow
transplantation10 can result in the development of
CD8+ T cells that are capable of cytokine secretion yet
incapable of cell division. Although the provenance and exact phenotype of such CD8+ T cells remain unclear,10-16 such
a failure to proliferate is generally attributed to replicative
senescence resulting from continual stimulation by antigen and/or
cytokine. Indeed, it has been suggested that replicative
senescence17-21 or "clonal
exhaustion"22-24 of HIV-specific T cells may underlie
the inability of T-cell immunity to suppress virus adequately. Other
studies have suggested that deficiencies in HIV-specific
CD8+ T-cell function may arise from insufficient
CD4+ T-cell help25-28 or specific signaling
and cytotoxic functional defects.25,29,30
The phenotypes associated with replicatively senescent CD8+
T cells are not well defined31,32 but are generally
attributed to lack of CD28 or expression of CD577,30,33-36
and are thought to result in the inability of these CD8+ T
cells to proliferate.37,38 These T cells commonly are
found in individuals with chronic immune
activation,4,6-10,39,40 and they increase in frequency
with age.41,42 We examined the relationship between CD57
expression and 2 functional aspects of HIV-specific, CMV-specific, and
other CD8+ T cells: their ability to produce cytokines and
to proliferate in response to stimulation by cognate antigen. We found
that CD57+ HIV-specific CD8+ T cells,
irrespective of CD28 or CCR7 expression, produce IFN- Study subjects
Peptides
Identification of HIV-specific CD8+ T cells (6-hour assay) Peripheral blood mononuclear cells (PBMCs) were isolated and, in some instances, viably cryopreserved until later use. Stimulation was performed on fresh or frozen PBMCs as previously described.43,44 In every experiment a negative control (anti-CD28/CD49d) was included to control for spontaneous production of IFN- , as well as a positive control (Staphylococcus
enterotoxin B (SEB) 1 µg/mL final, Sigma, St Louis, MO) to ensure
that cells were responsive. Cultures were incubated for 1 hour at
37°C, followed by an additional 5 hours in the presence of
Brefeldin-A (BFA) (1 µg/mL, Sigma). CD8+ T cells that
produce effector cytokines following antigenic-specific stimulation are
contained within and are thought to represent the tetramer-binding
CD8+ T cells.43,45-47
Antigen-specific proliferation (48-hour assay) PBMCs were initially stained with carboxyfluorescein diacetate succinimidyl ester (CFSE; Molecular Probes, Eugene, OR) as previously described.48 These PBMCs were suspended in media supplemented with IL-2 (10 U/mL, Sigma) or IL-15 (100 ng/mL, R&D Systems, Minneapolis, MN) and were then stimulated with HIV peptide pools as described.43,44 Cells were then incubated for 36 hours at 37°C followed by an additional 12 hours in the presence of Brefeldin-A (10 µg/mL, Sigma). Cells were then stained for flow cytometric analysis. The percentage of HIV-specific CD8+ T cells was determined as in the previous paragraph. The proportion of CD8+ T cells that showed CFSE dilution (division) at 48 hours was divided by 2 (a cell division represents a 2-fold increase in frequency, hence the percentage of proliferated CD8+ T cells must be halved) and then divided by the 6 hours' response; for instance ([1/2 48 hour divided response]/6 hours response). This number represents the percentage of antigen-specific CD8+ T cells that had divided in response to antigenic stimulation.Mitogen and superantigen stimulations For superantigen stimulations SEB (Sigma) was used at 1 µg/mL. For mitogenic stimulations phytohemagglutinin (PHA) (Sigma) was used at 5 µg/mL. PBMCs stimulated with SEB were cultured for 4 days prior to immunofluorescent staining, and PHA-stimulated PBMCs were cultured for 2 days prior to propidium iodide staining. For apoptosis studies, SEB-stimulated PBMCs were cultured for 24 hours in the presence of activated caspase 3 binding peptide Z-VK(biotin)D(OMe)-FMK at 43 µg/mL (Enzyme Systems Products, Livermore, CA).Immunofluorescence staining Stimulated PBMCs were washed and then surface stained with directly conjugated antibodies to CD3 and other surface markers (Becton Dickinson Immunocytometry Systems (BDIS), San Jose, CA) for 20 minutes on ice. The cells were washed and fix/permeabilized (fixation/permeabilization solution [BDIS]), and stained with directly conjugated antibodies to IFN- or other intracellular molecules (as required for specific experiments), and resuspended in
1% paraformaldehyde in phosphate-buffered saline.
Flow cytometric analysis Using a FACScalibur flow cytometer (BDIS), 6-parameter flow cytometric analysis was performed. Fluorescein isothiocyanate (FITC) or CFSE, PE, PerCP, and allophycocyanin (APCs) were used as the fluorophores. At least 100 000 live CD3+ lymphocytes were collected. Twelve-parameter flow cytometric analysis was performed using a modified FACSDIVA flow cytometer (BDIS). Alexa 430, FITC, PE, Texas-Red PE, Cy5PE, Cy5.5PE, Cy7PE, APC, Cy7APC, and Alexa 594 were used as fluorophores. The list-mode data files were analyzed using PAINT-A-GATE software (BDIS) and FlowJo software (Tree Star, San Carlos, CA). CFSE distributions were analyzed using FlowJo software.Cell sorting Cell sorting was accomplished using a FACSDiva cell sorter (BDIS). FITC, PE, Cy5PE, and APC were used as the fluorophores. At least 10 000 cells were sorted for PCR analysis, and at least 106 cells were sorted for telomere length and cell-division analysis.NK cells were magnetically sorted by a positive selection method with use of anti-CD16 antibodies conjugated to microbeads (Miltenyi Biotec, Auburn, CA). T-cell receptor excision circle analysis Quantification of T-cell receptor excision circle (TREC) in sorted CD8+ T cells was performed by real-time quantitative PCR by means of the 5' nuclease (TaqMan) assay with an ABI7700 system (PerkinElmer, Norwalk, CT) as previously described.49,50Telomere length analysis Telomere length analysis was performed using peptide nucleic acids (Dako, Carpinteria, CA) as previously described.51,52 Analysis was accomplished by comparing mean fluorescence intensity of the telomere channel between different populations that were all gated for similar DNA content (propidium iodide fluorescence) between samples.Statistical analysis Correlations were performed by Spearman rank correlation, and statistical significances were performed by Wilcoxon matched pairs test using Prism 3.0 software (San Diego, CA).
Proliferative defect in HIV-specific CD8+ T cells As functional defects of antigen-specific T cells in humans recently have been described in HIV infection, we analyzed antigen-specific CD8+ T-cell responses in healthy and HIV-infected subjects by IFN- secretion and proliferation by flow
cytometry. Figure 1A illustrates this
using PBMCs from a healthy HLA-A2+ individual (subject 31),
which we labeled with CFSE and stimulated with the HLA-A2-restricted
CMV pp65 peptide (NLVPMVATV). After 6 hours, 27% of CD8+ T
cells produced IFN- but had not divided. By 48 hours, 13% of the
CD8+ T cells had divided and continued to produce IFN-.
The percentage of responding CD8+ T cells and their ability
to proliferate were assessed also by tetramer analysis to assure that
the IFN--producing CD8+ T cells adequately represented
the antigen-specific CD8+ T cells (data not shown). Despite
this relatively high percentage of antigen-specific CD8+ T
cells, this response clearly demonstrated that the described assay
could be used to monitor proliferation in response to
antigenic stimulation.
To examine cytokine secretion and proliferation in HIV-specific
CD8+ T cells, we stimulated PBMCs from 11 HIV-infected
subjects with a pool of overlapping 15-mer peptides encompassing HIV
gag.43,45 In contrast to the CD8+ T-cell
proliferation observed for CMV-specific CD8+ T cells from
subject 31, a high proportion of HIV-specific CD8+ T cells
did not proliferate (Table 2). Three
patterns of responsiveness were apparent, as summarized in Figure 1B-D.
HIV gag-specific CD8+ T cells from subject 15 were capable
of proliferation and continued to produce IFN-
HIV-specific CD8+ T cells that do not proliferate are defined by CD57 expression Having determined the proliferative potential of the HIV-specific CD8+ T cells (Figure 1; Table 2), we sought to define phenotypic markers that might differentiate proliferating from nonproliferating HIV-specific CD8+ T cells (Table 2).As shown in Table 2, CD57 was the only surface marker we found that
alone defined the proliferative ability of HIV-specific CD8+ T cells (Figure 2; Table
2). In addition to surface molecules listed in Table 2, we also studied
expression patterns of CD152, CD11b, CD45RA, CD95, and CD45RO by
HIV-specific CD8+ T cells but found that these molecules
did not differ between T cells that proliferated and those that did
not. A recent study suggested that CCR7
We further confirmed the association between CD57 expression and
proliferative inability in 2 ways. First, in subject 15, whose
CD8+ T cells proliferated in response to HIV gag, all the
IFN- The presence of nondividing CD57+CD8+ T cells
specific for HIV gag correlated with that of
CD57+CD8+ T cells specific for HIV pol, env,
and nef (R = 0.95, P < .0001), suggesting that the
generation of such nondividing cells is related to the response to the
whole pathogen rather than to individual antigens (Figure
3A). In addition, the fraction of
HIV-specific CD8+ T cells that are CD57+
remained constant (the absolute number of CD57+
HIV-specific CD8+ T cells decreased) following highly
active antiretroviral therapy (data not shown). Figure 3B
demonstrates that CD57 expression by CD8+ T cells specific
for antigens other than HIV is only marginally correlated with
expression of CD57 by HIV-specific CD8+ T cells
(R = 0.58, P = .003). Whether this disparity is a result of differential cytokine expression by a significant proportion of
HIV-specific CD8+ T cells or an underestimation of
responses due to sequence differences or HIV accessory gene-specific
CD8+ T cells remains unclear. However, it is clear that
HIV-specific CD8+ T cells can contribute substantially (up
to 80%) to the total CD57+CD8+ T-cell
population in HIV-infected individuals.
We also investigated the effect of CD57 expression on all T-cell subsets by stimulating CFSE-labeled PBMCs from 2 HIV-infected individuals and 5 HIV-uninfected subjects with superantigen. No proliferation was observed within the CD57+CD8+ or CD57+CD4+ T cells. Furthermore, we studied proliferation of natural killer (NK) cells following stimulation with IL-2 and similarly found no proliferation within the NK cells, which expressed CD57 (data not shown). Hence, lack of proliferation by cells expressing CD57 is not restricted to HIV-specific CD57+CD8+ T cells but is a property of all T cells and NK cells. It has been described that CD57 and CD28 expression by CD8+
T cells are mutually exclusive.7,33,36,53 However, by
multiparameter flow cytometric analysis of memory CD8+ T
cells from 6 healthy subjects, we found that 4 populations of
CD8+ T cells were evident by CD28 and CD57 expression
(Figure 4). In all subjects there were
considerable levels of CD8+ T cells that were either
CD57+CD28+ or
CD57
It has been suggested that memory CD8+ T cells that
"revert" to a CD45RA+ phenotype represent a population
of terminally differentiated fully competent "effector memory" T
cells.30,54,55 In order to define further the
CD57+CD8+ T-cell population, we sought to
examine the relationship between expression of the markers that have
been used to define naive, "central memory," and effector memory
populations: CD57, CD27, CD28, CCR7, CD62L, CD45RO, and CD45RA. Figure
5 shows how we performed this using
10-color flow cytometry. Figure 5A shows that most of the effector
memory (CD45RA+CD27
CD57+ CD8+ T cells are characterized by replicative senescence The lack of proliferation of CD57+ HIV-specific and other CD8+ T cells suggests that they may have reached replicative senescence. Indeed, it has been shown that CD28 CD8+ T cells, the majority of which we
have shown are a subset of CD57+CD8+ T cells,
have shortened telomeres.19,41,56 To address this possibility, we examined the telomere lengths of CD57+ and
CD57 memory and naive CD8+ T cells in 3 healthy volunteers (representative plot in Figure 6A). The
CD57+CD8+ T cells had shorter telomeres than
either CD57 memory or naive CD8+ T cells.
Taken together, these results indicate that the
CD57+CD8+ T-cell population, as a whole, had
undergone more cell divisions than the
CD57CD8+ T-cell population. However, the
observed differences in telomere length between each subset, although
consistent from subject to subject, were small and did not reach
statistical significance.
In order to quantify proliferation differences between
CD57+ and memory CD57 Previous data have suggested that replicatively senescent T cells can
be defined by loss of CD28 expression.19,56,58 Because we
found discordance in proliferative ability within populations defined
by CD57 and CD28, we sought to determine the proliferative history of
each population defined in Figure 4. Hence, we sorted by flow
cytometry CD8+ T cells that were naive
CD45RO CD57+ CD8+ T cells are sensitive to induction of apoptosis The observation that CD57+ HIV-specific CD8+ T cells fail to proliferate and can no longer be detected by IFN- after 48 hours in vitro stimulation suggests that
these T cells might be undergoing activation-induced cell death.
Alternatively, they may remain in culture but fail to produce IFN-
at 48 hours. To address these possibilities, we used an HLA-A2 tetramer
complexed with an HLA-A2-restricted HIV gag peptide (amino acid
sequence SLYNTVATL) in an HLA-A2+ subject (subject 8) with
a response to this epitope and found that 51% of tetramer-binding
CD8+ T cells were CD57+. After stimulation with
SLYNTVATL peptide followed by a 48-hour incubation, only 11% of the
tetramer-binding CD8+ T cells were CD57+ (data
not shown), suggesting that the CD57+ tetramer binding
CD8+ T cells were no longer present in the culture.
To determine if CD57+CD8+ T cells were more
prone to undergo activation-induced cell death, we sorted
CD57+ and CD57
The cytokine IL-15 has been shown to reduce apoptosis59,60
and promote proliferation of HIV-specific CD8+ T
cells.61 However, we found that although IL-15
dramatically increased the percentage of proliferating
CD57
We have shown that HIV-specific CD8+ T cells that
express the surface molecule CD57 are incapable of proliferating after
antigen-specific stimulation in vitro and undergo activation-induced
apoptosis. Furthermore, this behavior is not associated with loss of
CD28 expression. Some studies have suggested that CD57 and CD28
expression are mutually exclusive in memory T-cell
populations.7,35,53,56 However, we found that
CD57+CD28+ and
CD57 CD57 expression is not limited to HIV-specific CD8+ T cells but is associated with the same properties among all T cells and NK cells. These data indicate that cells of both the adaptive arm as well as the innate arm of the immune system are capable of reaching a state of replicative senescence. From the very low TREC levels and the shortened telomere lengths in
CD57+CD8+ T cells, it is clear that this
population has undergone more rounds of replication in vivo than
CD57 While previous studies have suggested an inability of HIV-specific
CD8+ T cells to mature to
CD45RA+CCR7 Furthermore, CD8+ T cells belonging to the effector memory
population are defined as
CD45RA+CCR7 HIV-specific CD8+ T cells can contribute a large proportion (up to 80%) of the total CD57+ T cells, and there is a statistically significant correlation between the percentage of CD57+ HIV gag-specific CD8+ T cells and CD57+CD8+ T cells specific for other HIV antigens. Others have reported increased CD57 expression in persons with chronic CMV infection,9,36,64 even suggesting that all CD57+CD8+ T cells are specific for CMV antigens.65 Thus, the generation of replicative senescence of CD8+ T cells may occur as a result of repetitive antigenic stimulation in vivo by chronic persistent viruses such as CMV and HIV. Studies aimed at correlating HIV-specific CD8+ T-cell
responses with markers of HIV disease have resulted in different
conclusions.27,45,66-68 Whereas there is a negative
correlation between viral load and specific populations of bulk
CD57+CD8+ and
CD28 While the mechanism by which CD57 expression exerts these described phenotypes upon lymphocytes is unknown, and if CD57 is even, itself, involved in apoptosis and lack of proliferation is unknown, the proliferative defects and apoptotic nature observed within HIV-specific CD8+ T cells can be predicted by expression of CD57 on cells that have previously undergone multiple rounds of cell division. The presence of these cells, however, does not reflect a defect particular to the immune response to HIV or an effect limited to any particular virus, but simply reflects the normal consequence of persistent immune activation. Taken together, our data shed light on the functionality and provenance of CD57+ lymphocytes. Hence, in HIV disease, the presence of proliferation-incompetent HIV-specific CD8+ T cells is the result, not the cause, of uncontrolled viral replication. Although several conditions characterized by chronic antigenic stimulation may result in such an immune state, this underlying pathogenesis is a hallmark of untreated HIV infection.
Submitted July 15, 2002; accepted November 8, 2002.
Prepublished online as Blood First Edition Paper, November 14, 2002; DOI 10.1182/blood-2002-07-2103.
Supported by NIH grant AI49990 (N.J.K.) and RO1 AI47603 (N.J.K.), and the Distinguished Young Researcher Award from the UT Southwestern President's Research Council (N.J.K.).
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Richard A. Koup, Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, 40 Convent Dr, Bethesda, MD 20892; e-mail: rkoup{at}mail.nih.gov.
1.
Carmichael A, Jin X, Sissons P, Borysiewicz L.
Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein Barr virus in late disease.
J Exp Med.
1993;177:249-256 2. Kaech SM, Ahmed R. Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nat Immunol. 2001;2:415-422[Medline] [Order article via Infotrieve].
3.
Murali-Krishna K, Ahmed R.
Cutting edge: naive T cells masquerading as memory cells.
J Immunol.
2000;165:1733-1737 4. Wang EC, Lawson TM, Vedhara K, Moss PA, Lehner PJ, Borysiewicz LK. CD8high+ (CD57+) T cells in patients with rheumatoid arthritis. Arthritis Rheum. 1997;40:237-248[Medline] [Order article via Infotrieve]. 5. Schmidt D, Goronzy JJ, Weyand CM. CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest. 1996;97:2027-2037[Medline] [Order article via Infotrieve]. 6. Warrington KJ, Takemura S, Goronzy JJ, Weyand CM. CD4+, CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum. 2001;44:13-20[CrossRef][Medline] [Order article via Infotrieve].
7.
Sze DM, Giesajtis G, Brown RD, et al.
Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8(+)CD57(+)CD28(-) compartment.
Blood.
2001;98:2817-2827 8. Wang EC, Borysiewicz LK. The role of CD8+, CD57+ cells in human cytomegalovirus and other viral infections. Scand J Infect Dis. 1995;99(suppl):69-77. 9. Evans TG, Kallas EG, Luque AE, Menegus M, McNair C, Looney RJ. Expansion of the CD57 subset of CD8 T cells in HIV-1 infection is related to CMV serostatus. AIDS. 1999;13:1139-1141[CrossRef][Medline] [Order article via Infotrieve]. 10. Rowbottom AW, Garland RJ, Lepper MW, et al. Functional analysis of the CD8+CD57+ cell population in normal healthy individuals and matched unrelated T-cell-depleted bone marrow transplant recipients. Br J Haematol. 2000;110:315-321[CrossRef][Medline] [Order article via Infotrieve]. 11. Vingerhoets JH, Vanham GL, Kestens LL, et al. Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects. Clin Exp Immunol. 1995;100:425-433[Medline] [Order article via Infotrieve]. 12. Kern F, Khatamzas E, Surel I, et al. Distribution of human CMV-specific memory T cells among the CD8+ subsets defined by CD57, CD27, and CD45 isoforms. Eur J Immunol. 1999;29:2908-2915[CrossRef][Medline] [Order article via Infotrieve]. 13. Sadat-Sowti B, Debre P, Idziorek T, et al. A lectin-binding soluble factor released by CD8+CD57+ lymphocytes from AIDS patients inhibits T cell cytotoxicity. Eur J Immunol. 1991;21:737-741[Medline] [Order article via Infotrieve]. 14. Coakley G, Iqbal M, Brooks D, Panayi GS, Lanchbury JS. CD8+, CD57+ T cells from healthy elderly subjects suppress neutrophil development in vitro: implications for the neutropenia of Felty's and large granular lymphocyte syndromes. Arthritis Rheum. 2000;43:834-843[CrossRef][Medline] [Order article via Infotrieve]. 15. Sadat-Sowti B, Debre P, Mollet L, et al. An inhibitor of cytotoxic functions produced by CD8+ CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients. Eur J Immunol. 1994;24:2882-2888[Medline] [Order article via Infotrieve]. 16. Frassanito MA, Silvestris F, Cafforio P, Dammacco F. CD8+/CD57 cells and apoptosis suppress T-cell functions in multiple myeloma. Br J Haematol. 1998;100:469-477[CrossRef][Medline] [Order article via Infotrieve]. 17. Wolthers KC, Miedema F. Telomeres and HIV-1 infection: in search of exhaustion. Trends Microbiol. 1998;6:144-147[CrossRef][Medline] [Order article via Infotrieve]. 18. Bestilny LJ, Gill MJ, Mody CH, Riabowol KT. Accelerated replicative senescence of the peripheral immune system induced by HIV infection. AIDS. 2000;14:771-780[CrossRef][Medline] [Order article via Infotrieve]. 19. Effros RB, Allsopp R, Chiu CP, et al. Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. AIDS. 1996;10:F17-F22[Medline] [Order article via Infotrieve].
20.
Palmer LD, Weng N, Levine BL, June CH, Lane HC, Hodes RJ.
Telomere length, telomerase activity, and replicative potential in HIV infection: analysis of CD4+ and CD8+ T cells from HIV-discordant monozygotic twins.
J Exp Med.
1997;185:1381-1386 21. Pommier JP, Gauthier L, Livartowski J, et al. Immunosenescence in HIV pathogenesis. Virology. 1997;231:148-154[CrossRef][Medline] [Order article via Infotrieve].
22.
Brander C, Goulder PJ, Luzuriaga K, et al.
Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in utero HIV-1 infection.
J Immunol.
1999;162:4796-4800
23.
Pantaleo G, Soudeyns H, Demarest JF, et al.
Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV infection.
Proc Natl Acad Sci U S A.
1997;94:9848-9853 24. Soudeyns H, Pantaleo G. New mechanisms of viral persistence in primary human immunodeficiency virus (HIV) infection. J Biol Regul Homeost Agents. 1997;11:37-39[Medline] [Order article via Infotrieve].
25.
Ostrowski MA, Justement SJ, Ehler L, et al.
The role of CD4(+) T cell help and CD40 ligand in the in vitro expansion of HIV-1-specific memory cytotoxic CD8(+) T cell responses.
J Immunol.
2000;165:6133-6141
26.
Kalams SA, Walker BD.
The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses.
J Exp Med.
1998;188:2199-2204
27.
Rosenberg E, Billingsley J, Caliendo A, et al.
Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.
Science.
1997;278:1447-1450 28. Rosenberg ES, Walker BD. HIV type 1-specific helper T cells: a critical host defense. AIDS Res Hum Retroviruses. 1998;14(suppl 2):S143-S147.
29.
Appay V, Nixon DF, Donahoe SM, et al.
HIVspecific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function.
J Exp Med.
2000;192:63-75 30. Champagne P, Ogg GS, King AS, et al. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature. 2001;410:106-111[CrossRef][Medline] [Order article via Infotrieve].
31.
Voehringer D, Blaser C, Brawand P, Raulet DH, Hanke T, Pircher H.
Viral infections induce abundant numbers of senescent CD8 T cells.
J Immunol.
2001;167:4838-4843
32.
Mollet L, Sadat-Sowti B, Duntze J, et al.
CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity.
Int Immunol.
1998;10:311-323
33.
Kern F, Ode-Hakim S, Vogt K, Hoflich C, Reinke P, Volk HD.
The enigma of CD57+CD28- T cell expansion
34.
Hamann D, Kostense S, Wolthers KC, et al.
Evidence that human CD8+CD45RA+CD27- cells are induced by antigen and evolve through extensive rounds of division.
Int Immunol.
1999;11:1027-1033 35. Bandres E, Merino J, Vazquez B, et al. The increase of IFN-gamma production through aging correlates with the expanded CD8(+high)CD28(-) CD57(+) subpopulation. Clin Immunol. 2000;96:230-235[CrossRef][Medline] [Order article via Infotrieve]. 36. Weekes MP, Wills MR, Mynard K, Hicks R, Sissons JG, Carmichael AJ. Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population. Immunology. 1999;98:443-449[CrossRef][Medline] [Order article via Infotrieve]. 37. Lewis DE, Tang DS, Adu-Oppong A, Schober W, Rodgers JR. Anergy and apoptosis in CD8+ T cells from HIV-infected persons. J Immunol. 1994;153:412-420[Abstract]. 38. Lloyd TE, Yang L, Tang DN, Bennett T, Schober W, Lewis DE. Regulation of CD28 costimulation in human CD8+ T cells. J Immunol. 1997;158:1551-1558[Abstract].
39.
Jaffe JS, Strober W, Sneller MC.
Functional abnormalities of CD8+ T cells define a unique subset of patients with common variable immunodeficiency.
Blood.
1993;82:192-201 40. Namekawa T, Wagner UG, Goronzy JJ, Weyand CM. Functional subsets of CD4 T cells in rheumatoid synovitis. Arthritis Rheum. 1998;41:2108-2116[CrossRef][Medline] [Order article via Infotrieve]. 41. Tarazona R, DelaRosa O, Alonso C, et al. Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells. Mech Ageing Dev. 2000;121:77-88[CrossRef][Medline] [Order article via Infotrieve]. 42. Weyand CM, Brandes JC, Schmidt D, Fulbright JW, Goronzy JJ. Functional properties of CD4+ CD28- T cells in the aging immune system. Mech Ageing Dev. 1998;102:131-147[CrossRef][Medline] [Order article via Infotrieve].
43.
Betts MR, Casazza JP, Patterson BA, et al.
Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype.
J Virol.
2000;74:9144-9151 44. Pitcher CJ, Quittner C, Peterson DM, et al. HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression. Nat Med. 1999;5:518-525[CrossRef][Medline] [Order article via Infotrieve].
45.
Betts M, Ambrozak D, Douek D, et al.
Analysis of total HIV-specific CD4+ and CD8+ T cell responses: relationship to viral load in untreated HIV infection.
J Virol.
2001;75:11983-11991
46.
Goulder PJR, Tang Y, Brander C, et al.
Functionally inert HIV-specific cytotoxic T lymphocytes do not play a major role in chronically infected adults and children.
J Exp Med.
2000;192:1819-1832 47. Murali-Krishna K, Altman JD, Suresh M, et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity. 1998;8:177-187[CrossRef][Medline] [Order article via Infotrieve]. 48. Karandikar NJ, Crawford MP, Yan X, et al. Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis. J Clin Inv. 2002;109:641-649[CrossRef][Medline] [Order article via Infotrieve]. 49. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690-695[CrossRef][Medline] [Order article via Infotrieve]. 50. Douek DC, Vescio RA, Betts MR, et al. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet. 2000;355:1875-1881[CrossRef][Medline] [Order article via Infotrieve]. 51. Lauzon W, Sanchez Dardon J, Cameron DW, Badley AD. Flow cytometric measurement of telomere length. Cytometry. 2000;42:159-164[CrossRef][Medline] [Order article via Infotrieve].
52.
Rufer N, Brummendorf TH, Kolvraa S, et al.
Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood.
J Exp Med.
1999;190:157-167 53. Horiuchi T, Hirokawa M, Kawabata Y, et al. Identification of the T cell clones expanding within both CD8(+)CD28(+) and CD8(+)CD28(-) T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire. Bone Marrow Transplant. 2001;27:731-739[CrossRef][Medline] [Order article via Infotrieve]. 54. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708-712[CrossRef][Medline] [Order article via Infotrieve].
55.
Hamann D, Baars PA, Rep MH, et al.
Phenotypic and functional separation of memory and effector human CD8+ T cells.
J Exp Med.
1997;186:1407-1418 56. Monteiro J, Batliwalla F, Ostrer H, Gregersen PK. Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. J Immunol. 1996;156:3587-3590[Abstract].
57.
Kimmig S, Przybylski GK, Schmidt CA, et al.
Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood.
J Exp Med.
2002;195:789-794 58. Batliwalla F, Monteiro J, Serrano D, Gregersen PK. Oligoclonality of CD8+ T cells in health and disease: aging, infection, or immune regulation? Hum Immunol. 1996;48:68-76[CrossRef][Medline] [Order article via Infotrieve].
59.
Ku CC, Murakami M, Sakamoto A, Kappler J, Marrack P.
Control of homeostasis of CD8+ memory T cells by opposing cytokines.
Science.
2000;288:675-678 60. Manjunath N, Shankar P, Wan J, et al. Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. J Clin Invest. 2001;108:871-878[CrossRef][Medline] [Order article via Infotrieve]. 61. Kanai T, Thomas EK, Yasutomi Y, Letvin NL. IL-15 stimulates the expansion of AIDS virus-specific CTL. J Immunol. 1996;157:3681-3687[Abstract]. 62. Borthwick NJ, Bofill M, Gombert WM, et al. Lymphocyte activation in HIV-1 infection, II: functional defects of CD28- T cells. AIDS. 1994;8:431-441[Medline] [Order article via Infotrieve].
63.
Vallejo AN, Brandes JC, Weyand CM, Goronzy JJ.
Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence.
J Immunol.
1999;162:6572-6579 64. Wang EC, Taylor-Wiedeman J, Perera P, Fisher J, Borysiewicz LK. Subsets of CD8+, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses. Clin Exp Immunol. 1993;94:297-305[Medline] [Order article via Infotrieve]. 65. Wang EC, Moss PA, Frodsham P, Lehner PJ, Bell JI, Borysiewicz LK. CD8highCD57+ T lymphocytes in normal, healthy individuals are oligoclonal and respond to human cytomegalovirus. J Immunol. 1995;155:5046-5056[Abstract].
66.
Ogg GS, Jin X, Bonhoeffer S, et al.
Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.
Science.
1998;279:2103-2106
67.
Dalod M, Dupuis M, Deschemin JC, et al.
Broad, intense anti-human immunodeficiency virus (HIV) ex vivo CD8(+) responses in HIV type 1-infected patients: comparison with anti-Epstein-Barr virus responses and changes during antiretroviral therapy.
J Virol.
1999;73:7108-7116
68.
Gea-Banacloche JC, Migueles SA, Martino L, et al.
Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors.
J Immunol.
2000;165:1082-1092 69. Lieberman J, Trimble LA, Friedman RS, et al. Expansion of CD57 and CD62L-CD45RA+ CD8 T lymphocytes correlates with reduced viral plasma RNA after primary HIV infection. AIDS. 1999;13:891-899[CrossRef][Medline] [Order article via Infotrieve].
© 2003 by The American Society of Hematology.
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  C. Petrovas, B. Chaon, D. R. Ambrozak, D. A. Price, J. J. Melenhorst, B. J. Hill, C. Geldmacher, J. P. Casazza, P. K. Chattopadhyay, M. Roederer, et al. Differential Association of Programmed Death-1 and CD57 with Ex Vivo Survival of CD8+ T Cells in HIV Infection J. Immunol., July 15, 2009; 183(2): 1120 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Burgers, C. Riou, M. Mlotshwa, P. Maenetje, D. de Assis Rosa, J. Brenchley, K. Mlisana, D. C. Douek, R. Koup, M. Roederer, et al. Association of HIV-Specific and Total CD8+ T Memory Phenotypes in Subtype C HIV-1 Infection with Viral Set Point J. Immunol., April 15, 2009; 182(8): 4751 - 4761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Harari, F. B. Enders, C. Cellerai, P.-A. Bart, and G. Pantaleo Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure J. Virol., April 1, 2009; 83(7): 2862 - 2871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Chattopadhyay, M. R. Betts, D. A. Price, E. Gostick, H. Horton, M. Roederer, and S. C. De Rosa The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression J. Leukoc. Biol., January 1, 2009; 85(1): 88 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ladell, M. K. Hellerstein, D. Cesar, R. Busch, D. Boban, and J. M. McCune Central Memory CD8+ T Cells Appear to Have a Shorter Lifespan and Reduced Abundance as a Function of HIV Disease Progression J. Immunol., June 15, 2008; 180(12): 7907 - 7918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Barcy, S. C. De Rosa, J. Vieira, K. Diem, M. Ikoma, C. Casper, and L. Corey {gamma}{delta}+ T Cells Involvement in Viral Immune Control of Chronic Human Herpesvirus 8 Infection J. Immunol., March 1, 2008; 180(5): 3417 - 3425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. V. Komanduri, L. S. St. John, M. de Lima, J. McMannis, S. Rosinski, I. McNiece, S. G. Bryan, I. Kaur, S. Martin, E. D. Wieder, et al. Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing Blood, December 15, 2007; 110(13): 4543 - 4551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Almeida, D. A. Price, L. Papagno, Z. A. Arkoub, D. Sauce, E. Bornstein, T. E. Asher, A. Samri, A. Schnuriger, I. Theodorou, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover J. Exp. Med., October 1, 2007; 204(10): 2473 - 2485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Genesca, T. Rourke, J. Li, K. Bost, B. Chohan, M. B. McChesney, and C. J. Miller Live Attenuated Lentivirus Infection Elicits Polyfunctional Simian Immunodeficiency Virus Gag-Specific CD8+ T Cells with Reduced Apoptotic Susceptibility in Rhesus Macaques that Control Virus Replication after Challenge with Pathogenic SIVmac239 J. Immunol., October 1, 2007; 179(7): 4732 - 4740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Luciano, M. M. Lederman, A. Valentin-Torres, D. A. Bazdar, and S. F. Sieg Impaired Induction of CD27 and CD28 Predicts Naive CD4 T Cell Proliferation Defects in HIV Disease J. Immunol., September 15, 2007; 179(6): 3543 - 3549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Rezvani, A. S. M. Yong, B. N. Savani, S. Mielke, K. Keyvanfar, E. Gostick, D. A. Price, D. C. Douek, and A. J. Barrett Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia Blood, September 15, 2007; 110(6): 1924 - 1932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Ballan, B.-A. N. Vu, B. R. Long, C. P. Loo, J. Michaelsson, J. D. Barbour, L. L. Lanier, A. A. Wiznia, J. Abadi, G. J. Fennelly, et al. Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease Severity J. Immunol., September 1, 2007; 179(5): 3362 - 3370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Simpson, G. D. Florida-James, C. Cosgrove, G. P. Whyte, S. Macrae, H. Pircher, and K. Guy High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects J Appl Physiol, July 1, 2007; 103(1): 396 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Northfield, C. P. Loo, J. D. Barbour, G. Spotts, F. M. Hecht, P. Klenerman, D. F. Nixon, and J. Michaelsson Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ TEMRA Cells in Early Infection Are Linked to Control of HIV-1 Viremia and Predict the Subsequent Viral Load Set Point J. Virol., June 1, 2007; 81(11): 5759 - 5765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saez-Cirion, C. Lacabaratz, O. Lambotte, P. Versmisse, A. Urrutia, F. Boufassa, F. Barre-Sinoussi, J.-F. Delfraissy, M. Sinet, G. Pancino, et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype PNAS, April 17, 2007; 104(16): 6776 - 6781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Focosi and M. Petrini CD57 Expression on Lymphoma Microenvironment As a New Prognostic Marker Related to Immune Dysfunction J. Clin. Oncol., April 1, 2007; 25(10): 1289 - 1291. [Full Text] [PDF]
|
|
|
|
|
|
N. Khan, D. Best, R. Bruton, L. Nayak, A. B. Rickinson, and P. A. H. Moss T Cell Recognition Patterns of Immunodominant Cytomegalovirus Antigens in Primary and Persistent Infection J. Immunol., April 1, 2007; 178(7): 4455 - 4465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hoji, N. C. Connolly, W. G. Buchanan, and C. R. Rinaldo Jr. CD27 and CD57 Expression Reveals Atypical Differentiation of Human Immunodeficiency Virus Type 1-Specific Memory CD8+ T Cells Clin. Vaccine Immunol., January 1, 2007; 14(1): 74 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Casazza, M. R. Betts, D. A. Price, M. L. Precopio, L. E. Ruff, J. M. Brenchley, B. J. Hill, M. Roederer, D. C. Douek, and R. A. Koup Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation J. Exp. Med., December 25, 2006; 203(13): 2865 - 2877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Carr, M. J. Carrasco, J. E. D. Thaventhiran, P. J. Bambrough, M. Kraman, A. D. Edwards, A. Al-Shamkhani, and D. T. Fearon CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation PNAS, December 19, 2006; 103(51): 19454 - 19459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Le Priol, D. Puthier, C. Lecureuil, C. Combadiere, P. Debre, C. Nguyen, and B. Combadiere High Cytotoxic and Specific Migratory Potencies of Senescent CD8+CD57+ Cells in HIV-Infected and Uninfected Individuals J. Immunol., October 15, 2006; 177(8): 5145 - 5154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Petrovas, J. P. Casazza, J. M. Brenchley, D. A. Price, E. Gostick, W. C. Adams, M. L. Precopio, T. Schacker, M. Roederer, D. C. Douek, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection J. Exp. Med., October 2, 2006; 203(10): 2281 - 2292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Campillo, J. A. Martinez-Escribano, M. R. Moya-Quiles, L. A. Marin, M. Muro, N. Guerra, A. Parrado, M. Campos, J. F. Frias, A. Minguela, et al. Natural Killer Receptors on CD8 T Cells and Natural Killer Cells from Different HLA-C Phenotypes in Melanoma Patients. Clin. Cancer Res., August 15, 2006; 12(16): 4822 - 4831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Brenchley, L. E. Ruff, J. P. Casazza, R. A. Koup, D. A. Price, and D. C. Douek Preferential Infection Shortens the Life Span of Human Immunodeficiency Virus-Specific CD4+ T Cells In Vivo J. Virol., July 15, 2006; 80(14): 6801 - 6809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Munks, K. S. Cho, A. K. Pinto, S. Sierro, P. Klenerman, and A. B. Hill Four Distinct Patterns of Memory CD8 T Cell Responses to Chronic Murine Cytomegalovirus Infection J. Immunol., July 1, 2006; 177(1): 450 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Duvall, A. Jaye, T. Dong, J. M. Brenchley, A. S. Alabi, D. J. Jeffries, M. van der Sande, T. O. Togun, S. J. McConkey, D. C. Douek, et al. Maintenance of HIV-Specific CD4+ T Cell Help Distinguishes HIV-2 from HIV-1 Infection. J. Immunol., June 1, 2006; 176(11): 6973 - 6981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Tennakoon, R. S. Mehta, S. B. Ortega, V. Bhoj, M. K. Racke, and N. J. Karandikar Therapeutic Induction of Regulatory, Cytotoxic CD8+ T Cells in Multiple Sclerosis. J. Immunol., June 1, 2006; 176(11): 7119 - 7129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Schacker, J. M. Brenchley, G. J. Beilman, C. Reilly, S. E. Pambuccian, J. Taylor, D. Skarda, M. Larson, D. C. Douek, and A. T. Haase Lymphatic Tissue Fibrosis Is Associated with Reduced Numbers of Naive CD4+ T Cells in Human Immunodeficiency Virus Type 1 Infection. Clin. Vaccine Immunol., May 1, 2006; 13(5): 556 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-R. Kim, M. S. Hong, J. M. Dan, and I. Kang Altered IL-7R{alpha} expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses Blood, April 1, 2006; 107(7): 2855 - 2862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Islam, S. Y. Thomas, C. Hess, B. D. Medoff, T. K. Means, C. Brander, C. M. Lilly, A. M. Tager, and A. D. Luster The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in humans Blood, January 15, 2006; 107(2): 444 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Baeten, S. Louis, C. Braud, C. Braudeau, C. Ballet, F. Moizant, A. Pallier, M. Giral, S. Brouard, and J.-P. Soulillou Phenotypically and Functionally Distinct CD8+ Lymphocyte Populations in Long-Term Drug-Free Tolerance and Chronic Rejection in Human Kidney Graft Recipients J. Am. Soc. Nephrol., January 1, 2006; 17(1): 294 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Palmer, N. Blyveis, A. P. Fontenot, and C. C. Wilson Functional and Phenotypic Characterization of CD57+CD4+ T Cells and Their Association with HIV-1-Induced T Cell Dysfunction J. Immunol., December 15, 2005; 175(12): 8415 - 8423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Seth, D. Kaufmann, T. Lahey, E. S. Rosenberg, and K. W. Wucherpfennig Expansion and Contraction of HIV-Specific CD4 T Cells with Short Bursts of Viremia, but Physical Loss of the Majority of These Cells with Sustained Viral Replication J. Immunol., November 15, 2005; 175(10): 6948 - 6958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, X. Shen, J. Huang, R. J. Hodes, S. A. Rosenberg, and P. F. Robbins Telomere Length of Transferred Lymphocytes Correlates with In Vivo Persistence and Tumor Regression in Melanoma Patients Receiving Cell Transfer Therapy J. Immunol., November 15, 2005; 175(10): 7046 - 7052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Clay, D. S. Rodrigues, D. J. Harvey, C. M. Leutenegger, and U. Esser Distinct Chemokine Triggers and In Vivo Migratory Paths of Fluorescein Dye-Labeled T Lymphocytes in Acutely Simian Immunodeficiency Virus SIVmac251-Infected and Uninfected Macaques J. Virol., November 1, 2005; 79(21): 13759 - 13768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Amyes, A. J. McMichael, and M. F. C. Callan Human CD4+ T Cells Are Predominantly Distributed among Six Phenotypically and Functionally Distinct Subsets J. Immunol., November 1, 2005; 175(9): 5765 - 5773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U.-C. Meier, R. E. Owen, E. Taylor, A. Worth, N. Naoumov, C. Willberg, K. Tang, P. Newton, P. Pellegrino, I. Williams, et al. Shared Alterations in NK Cell Frequency, Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections J. Virol., October 1, 2005; 79(19): 12365 - 12374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Zaunders, M. L. Munier, D. E. Kaufmann, S. Ip, P. Grey, D. Smith, T. Ramacciotti, D. Quan, R. Finlayson, J. Kaldor, et al. Early proliferation of CCR5+ CD38+++ antigen-specific CD4+ Th1 effector cells during primary HIV-1 infection Blood, September 1, 2005; 106(5): 1660 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Miller, J. R. Bonczyk, Y. Nakayama, and M. Suresh Role of Thymic Output in Regulating CD8 T-Cell Homeostasis during Acute and Chronic Viral Infection J. Virol., August 1, 2005; 79(15): 9419 - 9429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Wherry, J. N. Blattman, and R. Ahmed Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination J. Virol., July 15, 2005; 79(14): 8960 - 8968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sacre, G. Carcelain, N. Cassoux, A.-M. Fillet, D. Costagliola, D. Vittecoq, D. Salmon, Z. Amoura, C. Katlama, and B. Autran Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease J. Exp. Med., June 20, 2005; 201(12): 1999 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Ibegbu, Y.-X. Xu, W. Harris, D. Maggio, J. D. Miller, and A. P. Kourtis Expression of Killer Cell Lectin-Like Receptor G1 on Antigen-Specific Human CD8+ T Lymphocytes during Active, Latent, and Resolved Infection and its Relation with CD57 J. Immunol., May 15, 2005; 174(10): 6088 - 6094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Almanzar, S. Schwaiger, B. Jenewein, M. Keller, D. Herndler-Brandstetter, R. Wurzner, D. Schonitzer, and B. Grubeck-Loebenstein Long-Term Cytomegalovirus Infection Leads to Significant Changes in the Composition of the CD8+ T-Cell Repertoire, Which May Be the Basis for an Imbalance in the Cytokine Production Profile in Elderly Persons J. Virol., March 15, 2005; 79(6): 3675 - 3683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Rock, S. M. Yoder, P. F. Wright, T. R. Talbot, K. M. Edwards, and J. E. Crowe Jr Differential Regulation of Granzyme and Perforin in Effector and Memory T Cells following Smallpox Immunization J. Immunol., March 15, 2005; 174(6): 3757 - 3764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Muraro, D. C. Douek, A. Packer, K. Chung, F. J. Guenaga, R. Cassiani-Ingoni, C. Campbell, S. Memon, J. W. Nagle, F. T. Hakim, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients J. Exp. Med., March 7, 2005; 201(5): 805 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sabbaj, M. K. Ghosh, B. H. Edwards, R. Leeth, W. D. Decker, P. A. Goepfert, and G. M. Aldrovandi Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans J. Immunol., March 1, 2005; 174(5): 2951 - 2956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Harari, F. Vallelian, P. R. Meylan, and G. Pantaleo Functional Heterogeneity of Memory CD4 T Cell Responses in Different Conditions of Antigen Exposure and Persistence J. Immunol., January 15, 2005; 174(2): 1037 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Knudson, S. Kulkarni, Z. K. Ballas, M. Bessler, and F. Goldman Association of immune abnormalities with telomere shortening in autosomal-dominant dyskeratosis congenita Blood, January 15, 2005; 105(2): 682 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Aandahl, M. F. Quigley, W. J. Moretto, M. Moll, V. D. Gonzalez, A. Sonnerborg, S. Lindback, F. M. Hecht, S. G. Deeks, M. G. Rosenberg, et al. Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment Blood, December 1, 2004; 104(12): 3672 - 3678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Wherry, D. L. Barber, S. M. Kaech, J. N. Blattman, and R. Ahmed Antigen-independent memory CD8 T cells do not develop during chronic viral infection PNAS, November 9, 2004; 101(45): 16004 - 16009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
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 N. Meidenbauer, A. Zippelius, M. J. Pittet, M. Laumer, S. Vogl, J. Heymann, M. Rehli, B. Seliger, S. Schwarz, F.-A. L. Gal, et al. High Frequency of Functionally Active Melan-A-Specific T Cells in a Patient with Progressive Immunoproteasome-Deficient Melanoma Cancer Res., September 1, 2004; 64(17): 6319 - 6326. [Abstract] [Full Text] [PDF]
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M. Nascimbeni, E.-C. Shin, L. Chiriboga, D. E. Kleiner, and B. Rehermann Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions Blood, July 15, 2004; 104(2): 478 - 486. [Abstract] [Full Text] [PDF]
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M. Lichterfeld, X. G. Yu, M. T. Waring, S. K. Mui, M. N. Johnston, D. Cohen, M. M. Addo, J. Zaunders, G. Alter, E. Pae, et al. HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8+ T cells producing both interferon-{gamma} and tumor necrosis factor-{alpha} Blood, July 15, 2004; 104(2): 487 - 494. [Abstract] [Full Text] [PDF]
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E. J. Wherry and R. Ahmed Memory CD8 T-Cell Differentiation during Viral Infection J. Virol., June 1, 2004; 78(11): 5535 - 5545. [Full Text] [PDF]
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M. P. Crawford, S. X. Yan, S. B. Ortega, R. S. Mehta, R. E. Hewitt, D. A. Price, P. Stastny, D. C. Douek, R. A. Koup, M. K. Racke, et al. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay Blood, June 1, 2004; 103(11): 4222 - 4231. [Abstract] [Full Text] [PDF]
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M. R. Betts, D. A. Price, J. M. Brenchley, K. Lore, F. J. Guenaga, A. Smed-Sorensen, D. R. Ambrozak, S. A. Migueles, M. Connors, M. Roederer, et al. The Functional Profile of Primary Human Antiviral CD8+ T Cell Effector Activity Is Dictated by Cognate Peptide Concentration J. Immunol., May 15, 2004; 172(10): 6407 - 6417. [Abstract] [Full Text] [PDF]
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J. Kan-Mitchell, B. Bisikirska, F. Wong-Staal, K. L. Schaubert, M. Bajcz, and M. Bereta The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope J. Immunol., May 1, 2004; 172(9): 5249 - 5261. [Abstract] [Full Text] [PDF]
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J. M. Brenchley, B. J. Hill, D. R. Ambrozak, D. A. Price, F. J. Guenaga, J. P. Casazza, J. Kuruppu, J. Yazdani, S. A. Migueles, M. Connors, et al. T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis J. Virol., February 1, 2004; 78(3): 1160 - 1168. [Abstract] [Full Text] [PDF]
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A. Larbi, N. Douziech, G. Dupuis, A. Khalil, H. Pelletier, K.-P. Guerard, and T. Fulop Jr Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes J. Leukoc. Biol., February 1, 2004; 75(2): 373 - 381. [Abstract] [Full Text] [PDF]
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L. M. Piliero, A. N. Sanford, D. M. McDonald-McGinn, E. H. Zackai, and K. E. Sullivan T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome Blood, February 1, 2004; 103(3): 1020 - 1025. [Abstract] [Full Text] [PDF]
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V. Jankovic, I. Messaoudi, and J. Nikolich-Zugich Phenotypic and functional T-cell aging in rhesus macaques (Macaca mulatta): differential behavior of CD4 and CD8 subsets Blood, November 1, 2003; 102(9): 3244 - 3251. [Abstract] [Full Text] [PDF]
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K. Rezvani, M. Grube, J. M. Brenchley, G. Sconocchia, H. Fujiwara, D. A. Price, E. Gostick, K. Yamada, J. Melenhorst, R. Childs, et al. Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation Blood, October 15, 2003; 102(8): 2892 - 2900. [Abstract] [Full Text] [PDF]
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Top
Abstract
Introduction
) and
CD57
)
(B). HIV-specific CD57+ (
CD28+CD57
CD28
anergy or activation?
Clin Exp Immunol.
1996;104:180-184