|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 715-718
BRIEF REPORT
C-C chemokine profile of cord blood mononuclear cells:
selective defect in RANTES production
Deepa Hariharan,
Wenzhe Ho,
Joann Cutilli,
Donald E. Campbell, and
Steven D. Douglas
From the Divisions of Neonatology and Immunologic and Infectious
Diseases and the Clinical Immunology Laboratories, The Children's
Hospital of Philadelphia, University of Pennsylvania School of
Medicine, Philadelphia, PA.
 |
Abstract |
Three C-C chemokines inhibit human immunodeficiency virus (HIV)
entry into macrophages: macrophage inflammatory protein-1 (MIP-1), MIP-1 , and regulated-upon activation, normal T-cell expressed and secreted (RANTES). We studied the ability of placental cord blood mononuclear cells (CBMC) to secrete these C-C chemokines in
comparison to adult blood mononuclear cells (ABMC). CBMC had diminished
ability to secrete RANTES, as determined by enzyme-linked immunosorbent
assay. Secretion of MIP-1 and MIP-1 were similar in CBMC and
ABMC. Whereas MIP-1 and MIP-1 secretion were comparable in
monocytes and lymphocytes, RANTES was secreted primarily by lymphocytes. Flow cytometric analysis of RANTES expression showed diminished intracellular RANTES expression in cord blood lymphocytes (CBL) compared to adult (peripheral) blood lymphocytes (ABL). A subset
analysis of RANTES-producing CBL and ABL demonstrated that RANTES was
produced predominantly by CD8+/CD45RO+ cells. CBL had a reduced
proportion of CD8+/CD45RO+ cells compared with ABL, which may
account for the diminished RANTES secretion by CBMC. These results may
be relevant to the pathogenesis of perinatal HIV infection.
(Blood. 2000;95:715-718)
© 2000 by The American Society of Hematology.
| |
Introduction |
Chemokines, a superfamily of polypeptide mediators, are
a key component of immune surveillance. The relative positions of the
cysteine tandem defines 4 classes of chemokines, the most important of
which are the C-C and the CXC chemokines. Chemokines bind to and
activate 7-transmembrane domain receptors. The C-C chemokines have a
broad spectrum of action and attract monocytes, lymphocytes,
eosinophils, basophils, and natural killer cells.1 The C-C
chemokines regulate leukocyte trafficking, inflammation, hematopoiesis,
antitumor immunity, and human immunodeficiency virus (HIV)
infection.1 In contrast, the CXC chemokines predominantly recruit neutrophils. While CXC chemokines, such as interleukin-8 (IL-8), claim a large and long history of experimental investigation, there is a paucity of information on C-C chemokine physiology in neonates.
The C-C chemokine receptor CCR5 is a major fusion coreceptor for HIV
infection of macrophages. Three C-C chemokines that are ligands for
CCR5 inhibit HIV entry into macrophages2-4: macrophage inflammatory protein-1 (MIP-1), MIP-1, and regulated-upon
activation, normal T-cell expressed and secreted (RANTES). Individuals
with high concentrations of these factors remain uninfected despite repeated exposure to HIV.5 Infants infected with HIV
perinatally have a more rapid and fatal course than older children and
adults because neonatal macrophages are more readily infected by HIV than are adult blood-derived macrophages.6,7 CD4 and CCR5 expression are similar in cord and adult blood mononuclear
phagocytes.6,8,9 It is thus possible that the differences
between HIV susceptiblity of neonatal and adult cells are due to
differences in the ability to secrete C-C chemokines. We investigated
and compared the in vitro abilities of placental cord blood mononuclear
cells (CBMC) and healthy adult blood mononuclear cells (ABMC) to
secrete the C-C chemokines MIP-1, MIP-1, and RANTES.
| |
Study design |
Cells
Mononuclear cells were isolated from the umbilical cord blood of
healthy term neonates and from the peripheral blood of healthy adult
donors by using density-gradient centrifugation of 1500g for 45 minutes over lymphocyte separation medium. Purified
monocyte and lymphocyte populations were isolated from the mononuclear cell layer using gelatin-coated flasks, and adherent monocytes were
detached with ethylene diamine tetra-acetic acid (EDTA).10 The purity of the cell populations thus isolated was >98% as
determined by immunofluorescence staining for CD14 and CD3 expression.
The cells were incubated in 24-well plates at a density of
1 × 106 cells/mL.
Enzyme-linked immunosorbent assay for C-C chemokines
MIP-1, MIP-1, and RANTES secretion in cord and adult blood was
compared using 3 groups of cells: CBMC and ABMC, purified cord blood
and adult blood lymphocytes (CBL and ABL), and purified monocytes.
CBMC, ABMC, CBL, and ABL cells were incubated for 24-96 hours either in
the resting state or with phorbol 12-myristate 13-acetate (PMA, 5 ng/mL). Monocytes from cord and adult blood were incubated with or
without lipopolysaccharide (LPS, 5 ng/mL) at 37°C with 5%
CO2 for 24-96 hours. At the completion of the incubation
period, the supernatants were stored at -70°C, and enzyme-linked
immunoabsorbent assay (ELISA) was performed in batches, as
described by the manufacturer (R&D Systems, Minneapolis, MN).
Intracellular analysis of RANTES expression
CBL and ABL were either unstimulated or stimulated with PMA (5 ng/mL) for 12 hours in the presence of monensin (2 µmol/L) (Golgistop; PharMingen, San Diego, CA) to inhibit protein transport and
secretion.11 For 2-color flow cytometry,
2 × 105 CBL or ABL were initially stained with
fluorescein-conjugated (FITC-conjugated) monoclonal antibodies (mAbs)
to the cell-surface markers CD4, CD8, CD45RA, or CD45RO (PharMingen) at
4°C for 30 minutes. For 3-color flow cytometry, CBL were stained
with cychrome-labeled CD4 or CD8 mAbs and FITC-labeled CD45RA or CD45RO
antibodies. After washing with 1 × phosphate-buffered saline
(PBS), the cells were fixed and permeabilized (Cytofix/Cytoperm
solution; PharMingen) according to the manufacturer's instructions.
Finally, the cells were incubated with phycoerythrin-conjugated
(PE-conjugated) mAb to human RANTES (PharMingen). Control antibodies
for the cell-surface markers and RANTES were isotype-matched.
Phenotypic analysis was performed on a flow cytometer
(EPICS-ELITE; Coulter Electronics, Hialeah, FL).
Statistical analysis
To mitigate the effects of any unrecognized day-to-day variations in
sample preparation or culture conditions, each cord blood sample was
paired with an adult blood sample that was processed simultaneously and
identically. Statistical analysis was done using the Student t
test for paired samples.
| |
Results and discussion |
Of the 3 C-C chemokines studied, only RANTES was secreted in the
constitutive phase by mononuclear cells and lymphocytes. CBMC and CBL
had significantly diminshed ability to secrete RANTES in the
constitutive phase, compared with ABMC and ABL, respectively (data not
shown). Monocytes did not show significant constitutive expression of
any of these chemokines. Even on induction with PMA, RANTES secretion
was significantly diminished in CBMC and CBL, compared with
PMA-stimulated ABMC and ABL, respectively (Figure 1). Study of kinetic changes in RANTES
secretion showed that RANTES secretion peaked at 24-30 hours in both
CBL and ABL (data not shown). MIP-1 and MIP-1 secretion were
similar in PMA-stimulated CBMC and ABMC (Figure 1). Whereas monocytes
from cord and adult blood showed similar levels of MIP-1 and
MIP-1 secretion, compared with ABL, CBL showed diminished ability to
secrete MIP-1 and MIP-1. MIP-1 and MIP-1 secretion were
comparable in monocytes and lymphocytes. However, monocytes were not a
significant source of RANTES in adult or cord blood (Figure 1). CBMC
comprised 8% to 38% monocytes compared with ABMC, which comprised 4%
to 16% monocytes. This finding may account for the relatively enhanced ability of CBMC to secrete MIP-1 and MIP-1 compared to RANTES. Thus, the selective defect in CBMC to secrete RANTES may be due to the
immaturity of CBL.
View larger version (31K):
[in this window]
[in a new window]
| Fig 1.
Secretion of C-C chemokines by cord and adult blood
cells.
MIP-1, MIP-1, and RANTES secretion in cord and adult blood were
compared using 3 groups of cells: CBMC and ABMC (n = 15 pairs);
purified lymphocytes CBL and ABL (n = 10 pairs); and purified
monocytes (n = 6 pairs). CBMC, ABMC, CBL, and ABL were
incubated with PMA (5 ng/mL) for 24 hours. Monocytes from
cord and adult blood were incubated with LPS (5 ng/mL) for 24 hours.
Results are shown as chemokine concentrations in the supernatants (mean ± SEM [standard error of mean]). *Indicates cord versus adult,
P < .05.
|
|
To allow for a more detailed and accurate comparison of a RANTES
profile in CBL and ABL, we used flow cytometry to study RANTES expression at the single-cell level. Intracellular
expression of RANTES in the resting phase and on stimulation with PMA
was significantly diminished in CBL compared to ABL (Figure
2A). In addition, constitutive expression
of RANTES was seen only in adult PBL. Thus, secretion of RANTES into
cell supernatants is concordant with intracellular RANTES expression in
lymphocytes, and the diminished ability of CBL to secrete RANTES is not
mainly due to defective secretory mechanisms.
View larger version (31K):
[in this window]
[in a new window]
| Fig 2.
Intracellular RANTES expression in CBL and ABL.
CBL and ABL were either untreated or stimulated with PMA (5 ng/mL) for
12 hours, after which staining for RANTES and the cell-surface markers
CD4, CD8, CD45RA, and CD45RO was performed as previously described. (A)
Flow cytometric RANTES expression in CBL and ABL. The shaded histograms
represent control staining with irrelevant mAb, and the open histograms
represent cells staining positive for RANTES. Percentages of cells
staining positive for RANTES are shown. (B) RANTES expression in
lymphocyte subsets (2-color flow cytometry). Results (mean ± SEM) are shown as percentages of cells in each subset expressing
RANTES and as relative fluorescence intensity (RFI = mean
fluorescence intensity of sample minus mean fluorescence intensity of
control/mean fluorescence intensity of control). The results are
representative of 6 pairs of cord and adult blood specimens. *Indicates
CD8 versus CD4, P < .05. **Indicates CD45RO versus
CD45RA, P < .05.
|
|
To further understand the mechanisms involved in the selective defect
in RANTES secretion by CBL, we performed subset analysis of
RANTES-expressing CBL and ABL using markers for helper and cytotoxic T
cells (CD4 and CD8, respectively) and for naive and memory T cells
(CD45RA and CD45RO, respectively). Two-color flow cytometry showed that
a significantly greater proportion of CD8+/CD45RO+ cells expressed
RANTES, compared with the RANTES expression of CD4+/CD45RA+ cells
(Figure 2B). Three-color flow cytometry on 3 cord blood specimens
showed that CD8+CD45RO+ and CD4+CD45RO+ CBL had
significantly higher RANTES expression than CD8+CD45RA+ and CD4+CD45RA+
CBL (data not shown).
We then compared the expression of CD4, CD8, CD45RA, and CD45RO in ABL
and CBL. In comparison to ABL, CBL had a reduced proportion of CD8+
cells and CD45RO+ cells. Mean counts are expressed as a
percentage of total lymphoid population: CD8+ cells: CBL,
18% ± 5%, and ABL, 30% ± 6% (P < .05);
CD45RO+ cells: CBL, 9% ± 2%, and ABL, 60% ± 7%
(P < .05). The majority of CBL were CD4+/CD45RA+ cells.
Mean counts are expressed as a percentage of total lymphoid population:
CD4+ cells: CBL, 42% ± 6%, and ABL,
54% ± 8%; CD45RA+ cells: CBL, 67% ± 8%, and ABL,
12% ± 3% (P < .05).
These figures are consistent with previous studies showing predominance
of naive or unprimed CD45RA+ cells and a relative deficiency of
cytotoxic/cytolytic CD8+ T cells in cord blood.12-14 Whereas CD45RA+ cells are the major source of cytokines, such as IL-2,
tumor necrosis factor- (TNF-), and interferon- (IFN-) in
cord blood,12 RANTES is secreted mainly by CD45RO+ cells in
cord blood. Our results indicate that the reduction of RANTES production in CBL may be due to the relative deficiency of CD8+/CD45RO+ cells.
Consistent with previous reports,15,16 we
observed higher total leukocyte counts in cord blood compared with
adult blood. We also observed relative neutrophilia and lymphopenia in
cord blood. CBL had mean total leukocyte counts of 18.4 ± 5.3
× 103/µL with 17%-30% lymphocytes. ABL had mean
total leukocyte counts of 11.4 ± 4.6
× 103/µL with 32%-44% lymphocytes. Thus,
absolute lymphocyte counts were only slightly higher in cord blood
compared to adult blood. This factor, in addition to the modestly
diminished proportion of CD8+ cells and markedly reduced proportion of
CD45RO+ cells in cord blood, resulted in lower absolute counts per
volume of RANTES-expressing T cells in cord blood compared to adult
blood (data not shown).
RANTES is a chemokine with a distinct physiologic role and a unique
mode of regulation.1 It is the only chemokine secreted in
the constitutive phase by T cells. Our results confirmed this finding
in ABL. However, CBL did not show constitutive RANTES expression.
RANTES recruits CD45RO+ cells and is the most potent chemoattractant
for CD8+ cells.1 Therefore, the ontogeny of RANTES
secretion may be relevant to the deficiency of CD8+/CD45RO+ cells in
neonates. RANTES acts as an antigen-independent activator of T cells,
mediating a spectrum of cellular responses such as calcium channel
opening, cytokine release, and IL-2 receptor expression.17 It also regulates eosinophil infiltration and activation and
induces histamine release from basophils. RANTES plays a key role in
allergic inflammation and has been implicated in conditions such as
bronchial asthma, chronic eosinophilic pneumonia,18,19 and
acute cardiac allograft rejection.20 The reduced incidence
of graft-versus-host disease in cord blood transplants14
may be in part due to the diminshed ability of neonatal cells to
secrete RANTES.
To our knowledge, there have been no previous reports comparing the
secretion of MIP-1, MIP-1, and RANTES by CBMC and ABMC. MIP-1,
MIP-1, and RANTES inhibit HIV entry into macrophages.21 Of the 3 C-C chemokines, RANTES was the most effective inhibitor of HIV infection of the PM1 cell line (CD4+
cell clone) and human peripheral blood mononuclear cells in
vitro.4 Whereas MIP-1 and MIP-1 had no inhibitory
effect on HIV infection of human alveolar macrophages when used singly,
RANTES by itself inhibited HIV infection in a dose-dependent
manner.22
Thus, RANTES plays a key role in modulating HIV infection of
mononuclear phagocytes. Suppression of HIV infection of macrophages occurs predominantly due to the combined effect of the 3 C-C
chemokines.2,4,5 Hence, a deficiency of RANTES
may diminish or neutralize the HIV-suppressive effect of MIP-1 and
MIP-1. In infants with perinatal exposure to HIV, significantly
higher levels of RANTES were observed in the sera of HIV-exposed
uninfected infants compared with HIV-infected infants, suggesting a
potential role for endogenous RANTES secretion in interrupting
perinatal transmission of acquired immunodeficiency syndrome
(AIDS).23 In HIV-infected infants, RANTES levels correlated with CD8 counts,23 a finding consistent with our results
showing that CD8+ cells are important sources of RANTES in cord blood. In addition, RANTES mediates HIV-specific T-cell cytotoxicity via the
chemokine receptor CCR3.24 Thus, it is possible that the
defect in RANTES secretion by neonatal cells may contribute to the
enhanced susceptibility of infants to overwhelming HIV infection and disease.
| |
Acknowledgments |
This research is supported by grants MOI RR00040, UO1 AI32921, and
R01 MH49981. The authors are grateful to Zanwei Xu and A. R. Reath
for technical and editorial assistance.
| |
Footnotes |
Submitted July 27, 1999; accepted September 15, 1999.
Reprints: Steven D. Douglas, Division of Immunologic and
Infectious Diseases, Abramson Research Building, Room 1208, The
Children's Hospital of Philadelphia, 34th Street and Civic Center
Blvd, Philadelphia, PA 19104; e-mail: douglas{at}emailchop.edu.
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.
| |
References |
1.
Rollins B.
Chemokines.
Blood.
1997;90:909-928[Free Full Text].
2.
Dragic T, Litwin V, Allaway GP, et al.
HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.
Nature.
1996;381:667-673[Medline]
[Order article via Infotrieve].
3.
Alkhatib G, Combadiere C, Broder CC, et al.
CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
Science.
1996;272:1955-1958[Abstract].
4.
Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P.
Identification of RANTES, MIP-1alpha, and MIP-1beta as the major HIV-suppressive factors produced by CD8+ T cells.
Science.
1995;270:1811-1815[Abstract/Free Full Text].
5.
Paxton WA, Martin SR, Tse D, et al.
Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures.
Nature Med.
1996;2:412-417[Medline]
[Order article via Infotrieve].
6.
Ho WZ, Lioy J, Song L, Cutilli JR, Polin RA, Douglas SD.
Infection of cord blood monocyte-derived macrophages with human immunodeficiency virus type 1.
J Virol.
1992;66:573-579[Abstract/Free Full Text].
7.
Sperduto AR, Bryson YJ, Chen ISY.
Increased susceptibility of neonatal monocyte/macrophages to HIV-1 infection.
AIDS Res Hum Retroviruses.
1993;9:1277-1285[Medline]
[Order article via Infotrieve].
8.
Hariharan D, Douglas SD, Lee B, Lai JP, Campbell DE, Ho WZ.
Interferon- upregulates CCR5 expression in cord and adult blood mononuclear phagocytes.
Blood.
1999;93:1137-1144[Abstract/Free Full Text].
9.
Fear WR, Kesson AM, Naif H, Lynch GW, Cunningham AL.
Differential tropism and chemokine receptor expression of human immunodeficiency virus type 1 in neonatal monocytes, monocyte-derived macrophages, and placental macrophages.
J Virol.
1998;72:1334-1344[Abstract/Free Full Text].
10.
Hassan NF, Cutilli JR, Douglas SD.
Isolation of highly purified human blood monocytes for in vitro HIV-1 infection studies of monocytes/macrophages.
J Immunol Methods.
1990;130:283-285[Medline]
[Order article via Infotrieve].
11.
Jung T, Schauer U, Heusser C, Neumann C, Reiger C.
Detection of intracellular cytokines by flow cytometry.
J Immunol Methods.
1993;159:197-207[Medline]
[Order article via Infotrieve].
12.
Chalmers IM, Janossy G, Contreras M, Navarrete C.
Intracellular cytokine profile of cord and adult blood lymphocytes.
Blood.
1998;92:11-33[Abstract/Free Full Text].
13.
Harris DT, Schumacher MJ, Losascio J, et al.
Phenotypic and functional immaturity of umbilical cord blood T lymphocytes.
Proc Natl Acad Sci U S A.
1992;89:10,006-10,010[Abstract/Free Full Text].
14.
Flomenberg N, Keever CA.
Cord blood transplants: Potential utility and potential limitations.
Bone Marrow Transpl.
1992;10:115-120.
15.
Nathan DG, Stuart HO.
Reference ranges for leukocyte counts in children. In:
Nathan DG,Oski, eds.
Hematology of Infancy and Childhood.Vol 2. Philadelphia: WB Saunders; 1998: Appendix XV.
16.
Hayward AR, Lee J, Beverly PC.
Ontogeny of expression of UCHL1 antigen on TcR-1+(CD4/8) and TcR delta+ T cells.
Eur J Immunol.
1989;19:771-773[Medline]
[Order article via Infotrieve].
17.
Bacon KB, Premack BA, Gardner P, Schall TJ.
Activation of dual T cell signaling pathways by the chemokine RANTES.
Science.
1995;269:1727-1730[Abstract/Free Full Text].
18.
Kuna P, Alam R, Ruta U, Gorski P.
RANTES induces nasal mucosal inflammation rich in eosinophils, basophils and lymphocytes in vivo.
Am J Respir Crit Care Med.
1998;157:873-879[Abstract/Free Full Text].
19.
Gonzalo JA, Lioyd CM, Wen D, et al.
The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness.
J Exp Med.
1998;188:157-167[Abstract/Free Full Text].
20.
Azzawi M, Hastleton PS, Geraghty PJ, et al.
RANTES chemokine expression is related to acute cardiac cellular rejection and infiltration by CD45RO T-lymphocytes and macrophages.
J Heart Lung Transplant.
1998;17:881887.
21.
Berger EA, Murphy PM, Farber JM.
Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism and disease.
Annu Rev Immuno.
1999;17:657-700[Medline]
[Order article via Infotrieve].
22.
Coffey MJ, Woffendin C, Phare SM, Strieter RM, Markowitz DM.
RANTES inhibits HIV-1 replication in human peripheral blood monocytes and alveolar macrophages.
Am J Physiol.
1997;272:L1025-L1029[Abstract/Free Full Text].
23.
Johann-Liang R, Varghese S, Gross K, Smith A, Cervia J, Noel GJ.
Elevated levels of beta chemokines in the sera of perinatally HIV-exposed but not-infected children <36 months [abstract].
Pediatr Res.
1998;43:149A.
24.
Hadida F, Vieillard V, Autran B, Clark-Lewis I, Baggiolini M, Debra P.
HIV-specific T cell cytotoxicity mediated by RANTES via the chemokine receptor CCR3.
J Exp Med.
1998;188:609-614[Abstract/Free Full Text].
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. A. Kaminski, S. Kadereit, R. E. Miller, P. Leahy, K. R. Stein, D. A. Topa, T. Radivoyevitch, M. L. Veigl, and M. J. Laughlin
Reduced expression of NFAT-associated genes in UCB versus adult CD4+ T lymphocytes during primary stimulation
Blood,
December 15, 2003;
102(13):
4608 - 4617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chaisavaneeyakorn, J. M. Moore, L. Mirel, C. Othoro, J. Otieno, S. C. Chaiyaroj, Y. P. Shi, B. L. Nahlen, A. A. Lal, and V. Udhayakumar
Levels of Macrophage Inflammatory Protein 1{alpha} (MIP-1{alpha}) and MIP-1{beta} in Intervillous Blood Plasma Samples from Women with Placental Malaria and Human Immunodeficiency Virus Infection
Clin. Vaccine Immunol.,
July 1, 2003;
10(4):
631 - 636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Shacklett, K. E. S. Shaw, L. A. Adamson, D. T. Wilkens, C. A. Cox, D. C. Montefiori, M. B. Gardner, P. Sonigo, and P. A. Luciw
Live, Attenuated Simian Immunodeficiency Virus SIVmac-M4, with Point Mutations in the Env Transmembrane Protein Intracytoplasmic Domain, Provides Partial Protection from Mucosal Challenge with Pathogenic SIVmac251
J. Virol.,
October 11, 2002;
76(22):
11365 - 11378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Losana, C. Bovolenta, L. Rigamonti, I. Borghi, F. Altare, E. Jouanguy, G. Forni, J.-L. Casanova, B. Sherry, M. Mengozzi, et al.
IFN-{gamma} and IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes
J. Leukoc. Biol.,
October 1, 2002;
72(4):
735 - 742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. King, R. Anderson, and J. S. Marshall
Dengue Virus Selectively Induces Human Mast Cell Chemokine Production
J. Virol.,
July 17, 2002;
76(16):
8408 - 8419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Muthumani, S. Kudchodkar, E. Papasavvas, L. J. Montaner, D. B. Weiner, and V. Ayyavoo
HIV-1 Vpr regulates expression of {beta} chemokines in human primary lymphocytes and macrophages
J. Leukoc. Biol.,
September 1, 2000;
68(3):
366 - 372.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Top
Abstract
Introduction