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PLENARY PAPER
From the University of Minnesota Cancer Center and
Department of Pediatrics, Division of Bone Marrow Transplantation,
Minneapolis.
Immune regulatory CD4+CD25+ cells
play a vital role in the induction and maintenance of self-tolerance
and the prevention of autoimmunity. Recently,
CD4+CD25+ cells have been shown to be required
for the ex vivo induction of tolerance to alloantigen via costimulatory
blockade and to inhibit allogeneic skin graft rejection. Data presented
here demonstrate that CD4+CD25+ cells play an
important role in graft-versus-host disease (GVHD) generation.
Depletion of CD4+CD25+ cells from the donor
T-cell inoculum or in vivo CD25-depletion of the recipient before
transplantation resulted in increased GVHD mediated by CD4+
or whole T cells in several strain combinations irrespective of the
total body irradiation conditioning regime. The infusion of freshly
purified donor CD4+CD25+ cells modestly
inhibited GVHD when administered in equal numbers with whole
CD4+ cells. Because CD4+CD25+ cells
only account for 5% to 10% of the total CD4+ population,
the administration of high numbers of fresh donor CD4+CD25+ cells may not be clinically
practical. However, we found that large numbers of
CD4+CD25+ cells can be obtained by ex
vivo activation and expansion. Cultured CD4+CD25+ cells, administered in equal numbers
with CD4+ T cells or CD25-depleted whole T cells, resulted
in significant inhibition of rapidly lethal GVHD. To our knowledge,
this study is the first to demonstrate that activated, cultured
CD4+CD25+ cells can offer substantial
protection in a relevant in vivo animal model of disease. These data
have important ramifications for clinical bone marrow and solid organ
transplantation. CD4+CD25+ cells warrant
consideration as an exciting new modality of cellular therapy for the
inhibition of undesirable autologous and allogeneic responses.
(Blood. 2002;99:3493-3499) Immune regulatory
CD4+CD25+ cells are essential for the induction
and maintenance of self-tolerance and for the prevention of autoimmunity. These thymically derived professional regulatory cells
prevent the activation and proliferation of autoreactive T cells that
have escaped thymic deletion or recognize extrathymic antigens. Elegant
studies by several investigators have elucidated their vital role in
T-cell homeostasis and immune regulation.1-9 Sakaguchi et
al1 found that the transfer of
CD4+CD25 The data presented here indicate that CD4+CD25+
cells play an important role in alloresponses in vivo, specifically
graft-versus-host disease (GVHD) generation. Ex vivo depletion of
CD4+CD25+ cells from the donor T-cell inoculum
or in vivo CD25 depletion of the recipient before transplantation
resulted in increased GVHD responses. These findings were observed
irrespective of the strain combinations, total body irradiation (TBI)
conditioning regime, and whether GVHD was mediated by CD4+
T cells or both CD4+ and CD8+ T cells. The
infusion of ex vivo-activated and -expanded donor CD4+CD25+ cells resulted in significant
inhibition of rapidly lethal GVHD. These data are the first to evaluate
the therapeutic efficacy of ex vivo-activated and -expanded
CD4+CD25+ regulatory cells in an in vivo animal
model of disease. We suggest that CD4+CD25+
cellular therapy warrants clinical consideration for the inhibition of
GVHD. Collectively, our and others' data indicate that
CD4+CD25+ immune regulatory cells will have an
exciting and expanding role in many areas of clinical immunology.
Mice
Cell enrichments and depletions
CD25+ ex vivo activation protocols Enriched CD25+ cells were suspended at a final concentration of 0.5 × 106 cells/mL in 24-well plates (Costar, Acton, MA) and cultured for 1 week. Culture media was Dulbecco modified Eagle medium (DMEM; Biowhittaker, Walkersville, MD) supplemented with 10% FBS (Hyclone), 50 mM 2-mercaptoethanol (Sigma, St Louis, MO), 10 mM Hepes buffer, 1 mM sodium pyruvate (Life Technologies, Grand Island, NY), amino acid supplements (1.5 mM L-glutamine, L-arginine, and L-asparagine; Sigma), and antibiotics (penicillin, 100 U/mL; streptomycin, 100 mg/mL; Sigma). Several conditions were tested. Condition 1 used soluble anti-CD3 (0.5 µg/mL; hybridoma 145-2C11, hamster IgG; BD Pharmingen) and recombinant human interleukin 2 (IL-2; 5.0 ng/mL; Amgen, Thousand Oaks, CA). Condition 2 used immobilized anti-CD3 (5.0 µg/mL and IL-2, 100 U/mL). Cells were removed from antibody-coated plates on day 3 and transferred to fresh plates and fed with IL-2-containing media. Condition 3 used irradiated allogeneic, host-type splenic stimulators to trigger the T-cell receptor (TCR) for activation and high-dose IL-2 (100 U/mL). Condition 4 was similar to condition 3 except that IL-2 was reduced to 10 U/mL and recombinant human transforming growth factor- 2
(TGF-2) was added as an additional growth factor
(1.0 ng/mL; R & D Systems, Minneapolis, MN).
GVHD induction In some experiments, bm12 recipients were sublethally irradiated by exposing mice to 6.0 Gy TBI from a 137Cs source at a dose rate of 85 cGy/min 4 hours prior to cell infusion. B6 CD4+ T cells were administered intravenously at the indicated cell number. In other experiments, recipients were lethally irradiated by x-ray on the day prior to transplantation with allogeneic, T cell-depleted bone marrow (BM) and either whole spleen or purified whole lymph node T cells or CD4+ T cells administered intravenously at the indicated cell dose. Where indicated, donor-type CD25+ cells were infused by separate intravenous injection. Where indicated, anti-CD25 mAb (hybridoma 7D4) was administered intravenously on day 10, 7, and 4 relative to day of
transplantation (0.5 mg antibody/injection). This dose and schedule
resulted in depletion of 60% to 70% of
CD4+CD25+ cells in lymph node and spleen when
examined 3 days after the last injection. Anti-CD25 mAb was partially
purified by ammonium sulfate precipitation of ascites produced in nude
mice. BALB/c SCID recipients were not irradiated but were depleted of
NK cells by intraperitoneal injection of 25 µL antiasialo GM1 (Wako
Chemicals, Richmond, VA) 2 and 4 days prior to allogeneic T-cell
transfer. Mice were monitored daily for survival and weighed twice
weekly as well as examined for the clinical appearance of GVHD.
Survival data were analyzed by life-table methods, and actuarial
survival rates are shown. Group comparisons were made by log-rank test statistics. P  .05 was considered significant.
Depletion of immune regulatory CD4+CD25+ cells results in acceleration of GVHD mortality in vivo In prior studies we demonstrated that CD4+CD25+ immune regulatory cells are required for the ex vivo induction of tolerance to alloantigen via costimulatory blockade.12 Furthermore, the addition of graded numbers of freshly purified B6 CD4+CD25+ cells resulted in the dose-dependent suppression of alloresponses in a mixed lymphocyte reaction composed of B6 CD4+CD25
responders and irradiated bm12 stimulators, whereas CD25 depletion of
CD4+ T cells resulted in a heightened
response.12 Those studies led us to further investigate
the potential role of these professional suppressor cells in regulating
T-cell responses to alloantigen and in generating GVHD. To
determine if depletion of CD25+ cells in a T-cell donor
inoculum would result in accelerated or increased GVHD mortality in
vivo, 105 whole B6 CD4+ T cells or
CD25-depleted B6 CD4+ T cells were administered to
sublethally irradiated bm12 recipients (Figure
1A). Recipients of CD25-depleted
CD4+ T cells died of GVHD 1 week earlier than recipients of
whole CD4+ cells (P = .024). Because
105 cells result in a rapid and highly lethal GVHD, the
experiment was repeated with a lower cell dose in an attempt to magnify
the difference in survival (Figure 1B). All recipients of
0.5 × 105 CD25-depleted CD4+ T cells
succumbed to GVHD by 19 days after infusion of cells. In contrast,
onset of GVHD was slower in recipients of whole CD4+ T
cells with 20% of mice surviving long-term (Figure 1B;
P = .0068).
To determine if the acceleration in GVHD mortality was either unique to
this strain combination or operative only under sublethal TBI
conditions, lethally irradiated BALB/c mice were recipients of B6 BM
and either whole CD4+ T cells or CD25-depleted
CD4+ T cells (Figure 2). All
recipients of CD25-depleted CD4+ T cells died by day 63 after transplantation (median survival = 35 days). In contrast, 25%
of mice receiving whole CD4+ T cells survived to day 100 (median survival = 91 days; Figure 2; P = .016). The
effect of CD25 depletion on GVHD generation was tested in 3 different
strain combinations where GVHD was mediated by both CD4+
and CD8+ T cells. In the first GVHD model, nonirradiated,
NK-depleted BALB/c SCID mice received whole T cells or CD25-depleted T
cells (Figure 3). CD25 depletion of the T
cells resulted in an acceleration of GVHD mortality (Figure 3;
P = .021) indicating that
CD4+CD25+ cells play a role in GVHD mediated by
both CD4+ and CD8+ T cells in the absence of
TBI conditioning. In a different strain combination, lethally
irradiated B10.BR mice received B6 BM and either whole B6 spleen or
CD25-depleted B6 spleen (Figure 4). Recipients of CD25-depleted spleen succumbed to GVHD mortality 10 days
earlier than recipients of whole spleen (P = .055). In a
third strain combination, B6 recipient mice were thymectomized prior to
transplantation to prevent the emergence of donor BM-derived CD4+CD25+ immune regulatory cells after
transplantation. Additionally, anti-CD25 mAb was administered to these
adult-thymectomized recipients before transplantation to deplete host
CD4+CD25+ regulatory cells in vivo. Anti-CD25
mAb-treated or control thymectomized B6 mice were lethally irradiated
and given BALB/c BM and whole spleen, and survival was monitored
(Figure 5). Mice treated with anti-CD25
mAb in vivo only prior to transplantation had a significantly lower
median survival rate as compared to controls (22 versus 44 days). All
anti-CD25 mAb-treated recipients succumbed to GVHD mortality by 28 days
after transplantation, 58 days earlier than control recipients (Figure
5; P = .0063). Collectively, these data indicate that
CD4+CD25+ immune regulatory cells play a
significant inhibitory role in GVHD generation regardless of strain
combination, pretransplant conditioning regime, or whether GVHD is
mediated by CD4+ T cells or by both CD4+ and
CD8+ T cells.
Infusion of ex vivo-activated and -expanded CD4+CD25+ immune regulatory cells ameliorates GVHD We hypothesized that the GVHD-protective effect of CD4+CD25+ cells could be clinically exploitable for the inhibition of GVHD lethality. However, previous data indicated that freshly purified CD4+CD25+ cells had only a very modest protective effect on GVHD when administered in a 1:1 ratio with whole CD4+ cells into sublethally irradiated major histocompatibility complex (MHC) class II-disparate recipients.12 Because CD4+CD25+ cells account for only 5% to 10% of the total CD4+ population in both mice and humans,13,14 the administration of sufficient numbers of freshly purified immune regulatory cells to be of significant therapeutic benefit may not be clinically practical. Because data indicate that CD4+CD25+ cells can become more potent suppressor cells on activation,15 we hypothesized that the ex vivo activation and expansion of CD4+CD25+ cells may make immune regulatory cellular therapy clinically more feasible. Initial attempts used ex vivo incubation of purified CD4+CD25+ cells with soluble anti-CD3 mAb, syngeneic antigen-presenting cells (APCs), and high-dose IL-2 (100 U/mL) as reported by others.15 Although cells expanded 10- to 15-fold with this protocol, suppressor function as measured after adoptive transfer in vivo was significantly impaired. Expanded activated CD4+CD25+ cells did not suppress GVHD when combined with equal numbers of fresh GVHD-inducing CD4+ T cells (data not shown). Additionally, in contrast to freshly isolated CD4+ T cells, control CD4+CD25 cells expanded under the same ex
vivo activation protocol failed to mediate lethality when injected into
allogeneic recipients, indicating that this expansion and activation
protocol resulted in a general loss of function in vivo (data not
shown). Therefore, we elected to modify the activation protocol to use
immobilized rather than soluble anti-CD3 mAb. After 3 days, cells were
removed from the antibody-coated plates to permit TCR re-expression,
and expanded in IL-2-containing media for an additional 4 days. This protocol resulted in a 15- to 20-fold expansion of
CD4+CD25+ cells. These expanded
CD25+ cells were evaluated in vivo for their capacity to
inhibit GVHD generation. Two million freshly purified B6
CD4+ T cells were infused into nonirradiated, NK-depleted
BALB/c SCID recipients. Cohorts of mice received a separate injection
of 2 × 106 activated CD4+CD25+
cells or CD4+CD25 cells, and survival and
weights were monitored (Figure 6 and data
not shown). The infusion of ex vivo-expanded CD25+ cells
significantly increased the median survival time from 10 days to 72 days (Figure 6; P = .022). Survival in mice receiving supplemental expanded CD25 cells was not significantly
different from control mice receiving only fresh CD4+ T
cells (Figure 6; P = .285), indicating that the protective effect was specific to the CD25+ population. Although the
administration of activated and expanded CD25+ cells
significantly prolonged survival, mice had substantial clinical
manifestations of GVHD (20% weight loss, diarrhea, hunched posture,
rough poor hair coat, and generalized erythema) and did eventually die
of GVHD. These data indicated that although CD25+ cells
could be expanded considerably ex vivo to obtain sufficient numbers to
significantly inhibit GVHD, additional improvements in the activation
and expansion protocol would need to be made to increase the
anti-GVHD effects.
In the next experiment, 3 different methods of activating and culturing
B6 CD25+ cells were compared. Condition 2, activation via
immobilized anti-CD3 and high-dose IL-2 (100 U/mL), as described above,
was used as a standard for comparison. Because immobilized antibody can
result in strong TCR signaling and activation-induced cell death,16-19 a less potent and global means of activation
was tested. Thus, in condition 3, irradiated BALB/c splenic stimulators
were added to purified B6 CD25+ cells (at a 2:1 ratio), to
induce more physiologic levels of TCR signaling and activation, and
cultured in the presence of high-dose IL-2 (100 U/mL). For condition 4, we hypothesized that although a relatively high dose of IL-2 might be
required for optimal expansion, withdrawal from high-dose IL-2 could be
contributing to poor cell survival on transfer in vivo thereby
potentially resulting in less than optimal GVHD
protection.16 To test this hypothesis, condition 4 used
irradiated BALB/c splenic stimulators and low-dose IL-2 (10 U/mL), and
TGF- An important part of the evaluation of the culturing conditions was the
recovery data because the clinical feasibility of this approach would
be dependent on being able to infuse sufficient numbers of activated
CD25+ regulatory cells. The culture protocol using
immobilized anti-CD3 and high-dose IL-2 resulted in a 12-fold expansion
of cells in 1 week. Irradiated allogeneic stimulators and high-dose
IL-2 led to only a 1.5-fold expansion of cells. The culture condition
using allogeneic splenic stimulators, low-dose IL-2, and
TGF- All 3 types of cultured CD25+ cells were evaluated for
their ability to inhibit GVHD mediated by both CD4+ and
CD8+ T cells (Figure 7).
BALB/c SCID mice received 106 CD25-depleted whole T cells
to induce GVHD. Two separate cohorts of mice also received
106 CD25+ cells cultured under each of the
first 2 conditions (anti-CD3/IL-2 or allo-APCs/IL-2). A third cohort
received 106 CD25-depleted whole T cells and
0.5 × 106 CD25+ cells cultured with
irradiated BALB/c splenocytes, low-dose IL-2, and TGF-
Although CD4+CD25+ immune regulatory cells are important regulators of in vivo homeostasis and are required for the prevention of autoimmunity, the role of these professional suppressor cells in alloresponses has been less well studied. The data presented here indicate that these professional cells also play an important role in the regulation of GVHD generation. This was demonstrated by the acceleration of GVHD and by the increase in lethality that occurred when CD25+ cells were depleted ex vivo from the donor T-cell inoculum or in vivo in the recipients before transplantation with anti-CD25 mAb infusion. Depletion of CD25+ cells resulted in an increase in GVHD regardless of whether donor antihost responses were mediated by CD4+ T cells or both CD4+ and CD8+ T cells. This is consistent with data by others that also found that CD4+CD25+ immune regulatory cells could inhibit CD8+ T-cell responses.21,22 Additionally, CD25+ cell depletion accelerated GVHD in several strain combinations irrespective of intensity of conditioning, indicating that even in a high proinflammatory cytokine milieu, CD25+ cells were functioning as suppressors of alloresponses. The depletion data implicated the role of CD25+ cells in inhibition of alloresponses and suggested that the infusion of CD25+ cells could prevent or ameliorate GVHD. Our previous data indicate that fresh naïve CD4+CD25+ cells did not mediate GVHD lethality alone and had only a modest protective effect when infused with GVHD-inducing T cells at a 1:1 ratio into sublethally irradiated MHC class II-disparate recipients.12 Because CD25+ cells constitute 5% to 10% of the total CD4+ T-cell population in human peripheral blood mononuclear cells,13,14 it would be difficult to infuse sufficient numbers of purified regulatory cells to be of significant therapeutic benefit. However, data by Thornton and Shevach indicate that CD4+CD25+ cells become more potent suppressor cells on ex vivo activation and furthermore cells can be significantly expanded during culture.15 Although the experiments presented in this paper used cells that were cultured for only 1 week, CD4+CD25+ cells can be expanded to an even greater degree with longer culture duration. A 67-fold expansion of CD4+CD25+ cells was obtained in 8 days in a recent experiment and cells have been maintained in culture for over 4 weeks (P. A. Taylor, unpublished data, 2001). The in vivo efficacy of such long-term cultured cells is yet to be determined. Data presented in this study indicate that different ex vivo activation
protocols led to varying recovery or expansion of CD4+CD25+ cells, but all protocols resulted in
cells that significantly inhibited GVHD albeit to varying degrees. The
ex vivo activation protocols investigated in these studies were meant
to demonstrate proof-of-principle and not to be an exhaustive list of
potential strategies for expansion and activation. Clearly, additional
studies designed to develop new activation and expansion approaches and to determine which of these approaches is the most effective in GVHD
prevention are warranted. For example,
CD4+CD25+ immune regulatory cells are a very
heterogeneous population. Therefore, it seems likely that different
methods of activation and expansion may result in distinct populations
of cells with potentially different suppressor/effector function.
Although the best protection (despite the lower number of infused
cells) was mediated by the culture method that resulted in the lowest
recovery (allogeneic splenocytes, low-dose IL-2, and TGF- An important contribution of these data is that the various GVHD models used allow for the evaluation of the in vivo therapeutic efficacy of activation and expansion protocols of CD4+CD25+ cells in a relevant animal model of disease. Because of the known potential deficits of activated cultured cells in homing, migration, survival, and function in vivo, it is important that the regulatory function of ex vivo activated and expanded regulatory cells be evaluated in vivo as well as in vitro. For example, although CD4+CD25+ cells can be activated and expanded via culture with soluble anti-CD3 mAb, APCs, and IL-2 (the current "gold standard" in ex vivo expansion protocols) and maintain in vitro suppressor function, their ability to suppress alloresponses was lost on in vivo transfer15 (data not shown). It is also important to note that although multiple cell doses were not examined in these studies, the ease of expansion of CD4+CD25+ cells will readily permit the infusion of much higher cell doses than those used for these experiments. Additionally, the infusion of expanded CD25+ cells as pretransplantation conditioning to inhibit either GVHD generation or graft rejection or the administration of multiple infusions after BM transplantation may also be of clinical benefit. Future experiments will address these issues. The mechanism by which activated CD25+ cells inhibit GVHD
remains unknown, but the literature suggests several possibilities that
are not necessarily mutually exclusive. Data from Nakamura et
al23 indicate that a culture protocol including immobilized anti-CD3 mAb and anti-CTLA4 mAb, soluble anti-CD28 mAb, and IL-2 led to
the highest production of cell surface-bound TGF- If we accept that CD4+CD25+ cells have a regulatory role in immune responses to foreign or alloantigen as well as in autoimmunity, the increase in GVHD lethality resulting from CD25 depletion of the donor T-cell inoculum might be anticipated. However, interpretation of the in vivo depletion data in which anti-CD25 mAb is administered to the recipient is potentially more complicated and suggests some intriguing possibilities that might be of clinical relevance. Anti-CD25 mAb was administered to the recipient before transplantation in an attempt to avoid depletion of host-reactive donor T cells that would up-regulate CD25 as an activation marker during GVHD. Although CD25 depletion after BM transplantation has been shown to ameliorate GVHD,28-31 CD25 depletion of the recipient before transplantation accelerated GVHD implicating host CD25+ cells as involved in dampening the GVHD response. Although the goal was to deplete host CD25+ cells and the last anti-CD25 mAb injection was given 4 days prior to transplantation, we cannot exclude the possibility that there was sufficient circulating antibody to deplete both host and donor CD25+ cells including donor CD4+CD25+ regulatory cells. However, because GVHD was worsened by the infusion of anti-CD25 mAb before transplantation, we hypothesize that residual host CD25+ cells remaining after radiation may also inhibit the generation of GVHD by the donor T-cell inoculum via a host antidonor resistance mechanism. This raises the rather intriguing speculation that either donor or host-type CD25+ cells could be used to inhibit GVHD responses and further suggests that maintenance of host CD25+ cells would be clinically desirable. Future studies will address these issues. These data also suggest that the clinical targeting of activated CD25+ donor T cells as a means to prevent GVHD may be complicated by the fact that potentially beneficial CD25+ immune regulatory cells could also be depleted. In summary, we show that CD4+CD25+ cells play an important role in alloresponses in vivo and in the generation of GVHD. Ex vivo expanded and activated immune regulatory cells significantly inhibited rapidly lethal GVHD. Because human CD4+CD25+ regulatory cells have been reported to inhibit in vitro alloresponses of both naïve and memory CD4+ T cells and can be expanded in vitro with maintenance of suppressor function,13,14,32 these preclinical data may be translatable. Collectively, these studies have important clinical ramifications in many areas of clinical immunology and transplantation biology.
The authors thank Drs Angela Thornton and Ethan Shevach for helpful advice on the purification and expansion of CD4+CD25+ T cells.
Submitted November 5, 2001; accepted January 7, 2002.
Supported by National Institutes of Health grants R01 AI34495, R37 HL56067, and PO1 AI 35225 to B.R.B.
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: Bruce R. Blazar, University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, MN 55455; e-mail: blaza001{at}tc.umn.edu.
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2001;193:1285-1294
© 2002 by The American Society of Hematology.
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  N. Beyersdorf, X. Ding, T. Hunig, and T. Kerkau Superagonistic CD28 stimulation of allogeneic T cells protects from acute graft-versus-host disease Blood, November 12, 2009; 114(20): 4575 - 4582. [Abstract] [Full Text] [PDF]
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C. H. Miao, B. R. Harmeling, S. F. Ziegler, B. C. Yen, T. Torgerson, L. Chen, R. J. Yau, B. Peng, A. R. Thompson, H. D. Ochs, et al. CD4+FOXP3+ regulatory T cells confer long-term regulation of factor VIII-specific immune responses in plasmid-mediated gene therapy-treated hemophilia mice Blood, November 5, 2009; 114(19): 4034 - 4044. [Abstract] [Full Text] [PDF]
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 J. K. Davies, L. M. Nadler, and E. C. Guinan Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation Science Translational Medicine, October 7, 2009; 1(1): 1ra3 - 1ra3. [Abstract] [Full Text] [PDF]
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D. Fowler T cells helping GVHD: take-away lessons Blood, October 1, 2009; 114(14): 2858 - 2859. [Full Text] [PDF]
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B. Blanco, J. A. Perez-Simon, L. I. Sanchez-Abarca, T. Caballero-Velazquez, S. Gutierrez-Cossio, P. Hernandez-Campo, M. Diez-Campelo, C. Herrero-Sanchez, C. Rodriguez-Serrano, C. Santamaria, et al. Treatment with bortezomib of human CD4+ T cells preserves natural regulatory T cells and allows the emergence of a distinct suppressor T-cell population Haematologica, July 1, 2009; 94(7): 975 - 983. [Abstract] [Full Text] [PDF]
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O. Bohana-Kashtan, S. Morisot, R. Hildreth, C. Brayton, H. I. Levitsky, and C. I. Civin Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand J. Immunol., July 1, 2009; 183(1): 696 - 705. [Abstract] [Full Text] [PDF]
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M. Bruinsma, P. L. van Soest, P. J. M. Leenen, B. Lowenberg, J. J. Cornelissen, and E. Braakman Keratinocyte Growth Factor Improves Allogeneic Bone Marrow Engraftment through a CD4+Foxp3+ Regulatory T Cell-Dependent Mechanism J. Immunol., June 15, 2009; 182(12): 7364 - 7369. [Abstract] [Full Text] [PDF]
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A. L. Bayer, M. Jones, J. Chirinos, L. de Armas, T. H. Schreiber, T. R. Malek, and R. B. Levy Host CD4+CD25+ T cells can expand and comprise a major component of the Treg compartment after experimental HCT Blood, January 15, 2009; 113(3): 733 - 743. [Abstract] [Full Text] [PDF]
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N. D. Verma, K. M. Plain, M. Nomura, G. T. Tran, C. Robinson, R. Boyd, S. J. Hodgkinson, and B. M. Hall CD4+CD25+ T cells alloactivated ex vivo by IL-2 or IL-4 become potent alloantigen-specific inhibitors of rejection with different phenotypes, suggesting separate pathways of activation by Th1 and Th2 responses Blood, January 8, 2009; 113(2): 479 - 487. [Abstract] [Full Text] [PDF]
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C. Vogtenhuber, M. J. O'Shaughnessy, D. A. A. Vignali, and B. R. Blazar Outgrowth of CD4low/negCD25+ T Cells with Suppressor Function in CD4+CD25+ T Cell Cultures upon Polyclonal Stimulation Ex Vivo J. Immunol., December 15, 2008; 181(12): 8767 - 8775. [Abstract] [Full Text] [PDF]
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W. Chen, X. Liang, A. J. Peterson, D. H. Munn, and B. R. Blazar The Indoleamine 2,3-Dioxygenase Pathway Is Essential for Human Plasmacytoid Dendritic Cell-Induced Adaptive T Regulatory Cell Generation J. Immunol., October 15, 2008; 181(8): 5396 - 5404. [Abstract] [Full Text] [PDF]
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K. L. Hippen, P. Harker-Murray, S. B. Porter, S. C. Merkel, A. Londer, D. K. Taylor, M. Bina, A. Panoskaltsis-Mortari, P. Rubinstein, N. Van Rooijen, et al. Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells Blood, October 1, 2008; 112(7): 2847 - 2857. [Abstract] [Full Text] [PDF]
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W. Tu, Y.-L. Lau, J. Zheng, Y. Liu, P.-L. Chan, H. Mao, K. Dionis, P. Schneider, and D. B. Lewis Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells Blood, September 15, 2008; 112(6): 2554 - 2562. [Abstract] [Full Text] [PDF]
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D. Zhao, C. Zhang, T. Yi, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, and D. Zeng In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease Blood, September 1, 2008; 112(5): 2129 - 2138. [Abstract] [Full Text] [PDF]
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R. Aricha, T. Feferman, S. Fuchs, and M. C. Souroujon Ex Vivo Generated Regulatory T Cells Modulate Experimental Autoimmune Myasthenia Gravis J. Immunol., February 15, 2008; 180(4): 2132 - 2139. [Abstract] [Full Text] [PDF]
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M. C. Ruzek, J. S. Waire, D. Hopkins, G. LaCorcia, J. Sullivan, B. L. Roberts, S. M. Richards, S. R. Nahill, J. M. Williams, A. Scaria, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo Blood, February 1, 2008; 111(3): 1726 - 1734. [Abstract] [Full Text] [PDF]
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J.-G. Chai, D. Coe, D. Chen, E. Simpson, J. Dyson, and D. Scott In Vitro Expansion Improves In Vivo Regulation by CD4+CD25+ Regulatory T Cells J. Immunol., January 15, 2008; 180(2): 858 - 869. [Abstract] [Full Text] [PDF]
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V. H. Nguyen, S. Shashidhar, D. S. Chang, L. Ho, N. Kambham, M. Bachmann, J. M. Brown, and R. S. Negrin The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation Blood, January 15, 2008; 111(2): 945 - 953. [Abstract] [Full Text] [PDF]
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M. Bruinsma, P. L. van Soest, P. J. M. Leenen, B. N. Lambrecht, T. Cupedo, B. Lowenberg, J. J. Cornelissen, and E. Braakman Keratinocyte Growth Factor Induces Expansion of Murine Peripheral CD4+Foxp3+ Regulatory T Cells and Increases Their Thymic Output J. Immunol., December 1, 2007; 179(11): 7424 - 7430. [Abstract] [Full Text] [PDF]
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J.-R. Pallandre, E. Brillard, G. Crehange, A. Radlovic, J.-P. Remy-Martin, P. Saas, P.-S. Rohrlich, X. Pivot, X. Ling, P. Tiberghien, et al. Role of STAT3 in CD4+CD25+FOXP3+ Regulatory Lymphocyte Generation: Implications in Graft-versus-Host Disease and Antitumor Immunity J. Immunol., December 1, 2007; 179(11): 7593 - 7604. [Abstract] [Full Text] [PDF]
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P. A. Taylor, M. J. Ehrhardt, C. J. Lees, J. Tolar, B. J. Weigel, A. Panoskaltsis-Mortari, J. S. Serody, V. Brinkmann, and B. R. Blazar Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD) Blood, November 1, 2007; 110(9): 3480 - 3488. [Abstract] [Full Text] [PDF]
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S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al. Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease Blood, September 1, 2007; 110(5): 1689 - 1697. [Abstract] [Full Text] [PDF]
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K. N. Taylor, V. R. Shinde-Patil, E. Cohick, and Y. L. Colson Induction of FoxP3+CD4+25+ Regulatory T Cells Following Hemopoietic Stem Cell Transplantation: Role of Bone Marrow-Derived Facilitating Cells J. Immunol., August 15, 2007; 179(4): 2153 - 2162. [Abstract] [Full Text] [PDF]
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R. Zeiser, V. H. Nguyen, J.-Z. Hou, A. Beilhack, E. Zambricki, M. Buess, C. H. Contag, and R. S. Negrin Early CD30 signaling is critical for adoptively transferred CD4+CD25+ regulatory T cells in prevention of acute graft-versus-host disease Blood, March 1, 2007; 109(5): 2225 - 2233. [Abstract] [Full Text] [PDF]
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J. Ochoa-Reparaz, C. Riccardi, A. Rynda, S. Jun, G. Callis, and D. W. Pascual Regulatory T Cell Vaccination without Autoantigen Protects against Experimental Autoimmune Encephalomyelitis J. Immunol., February 1, 2007; 178(3): 1791 - 1799. [Abstract] [Full Text] [PDF]
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D. Golshayan, S. Jiang, J. Tsang, M. I. Garin, C. Mottet, and R. I. Lechler In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance Blood, January 15, 2007; 109(2): 827 - 835. [Abstract] [Full Text] [PDF]
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P. Hoffmann, R. Eder, T. J. Boeld, K. Doser, B. Piseshka, R. Andreesen, and M. Edinger Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion Blood, December 15, 2006; 108(13): 4260 - 4267. [Abstract] [Full Text] [PDF]
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E. Zorn and J. Ritz Studying Human Regulatory T Cells In vivo. Clin. Cancer Res., September 15, 2006; 12(18): 5265 - 5267. [Full Text] [PDF]
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T. Mutis, R. S. van Rijn, E. R. Simonetti, T. Aarts-Riemens, M. E. Emmelot, L. van Bloois, A. Martens, L. F. Verdonck, and S. B. Ebeling Human Regulatory T Cells Control Xenogeneic Graft-versus-Host Disease Induced by Autologous T Cells in RAG2-/-{gamma}c-/- Immunodeficient Mice. Clin. Cancer Res., September 15, 2006; 12(18): 5520 - 5525. [Abstract] [Full Text] [PDF]
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K. Rezvani, S. Mielke, M. Ahmadzadeh, Y. Kilical, B. N. Savani, J. Zeilah, K. Keyvanfar, A. Montero, N. Hensel, R. Kurlander, et al. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT Blood, August 15, 2006; 108(4): 1291 - 1297. [Abstract] [Full Text] [PDF]
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K. J. Scalapino, Q. Tang, J. A. Bluestone, M. L. Bonyhadi, and D. I. Daikh Suppression of Disease in New Zealand Black/New Zealand White Lupus-Prone Mice by Adoptive Transfer of Ex Vivo Expanded Regulatory T Cells J. Immunol., August 1, 2006; 177(3): 1451 - 1459. [Abstract] [Full Text] [PDF]
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R. Zeiser, V. H. Nguyen, A. Beilhack, M. Buess, S. Schulz, J. Baker, C. H. Contag, and R. S. Negrin Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production Blood, July 1, 2006; 108(1): 390 - 399. [Abstract] [Full Text] [PDF]
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D. Adeegbe, A. L. Bayer, R. B. Levy, and T. R. Malek Cutting Edge: Allogeneic CD4+CD25+Foxp3+ T Regulatory Cells Suppress Autoimmunity while Establishing Transplantation Tolerance. J. Immunol., June 15, 2006; 176(12): 7149 - 7153. [Abstract] [Full Text] [PDF]
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A. Trenado, M. Sudres, Q. Tang, S. Maury, F. Charlotte, S. Gregoire, M. Bonyhadi, D. Klatzmann, B. L. Salomon, and J. L. Cohen Ex Vivo-Expanded CD4+CD25+ Immunoregulatory T Cells Prevent Graft-versus-Host-Disease by Inhibiting Activation/Differentiation of Pathogenic T Cells J. Immunol., January 15, 2006; 176(2): 1266 - 1273. [Abstract] [Full Text] [PDF]
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M. Firan, S. Dhillon, P. Estess, and M. H. Siegelman Suppressor activity and potency among regulatory T cells is discriminated by functionally active CD44 Blood, January 15, 2006; 107(2): 619 - 627. [Abstract] [Full Text] [PDF]
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K.-i. Matsuoka, T. Ichinohe, D. Hashimoto, S. Asakura, M. Tanimoto, and T. Teshima Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+CD25+ T-cell-dependent mechanism Blood, January 1, 2006; 107(1): 404 - 409. [Abstract] [Full Text] [PDF]
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M.-T. Lin, B. Storer, P. J. Martin, L.-H. Tseng, B. Grogan, P.-J. Chen, L. P. Zhao, and J. A. Hansen Genetic variation in the IL-10 pathway modulates severity of acute graft-versus-host disease following hematopoietic cell transplantation: synergism between IL-10 genotype of patient and IL-10 receptor {beta} genotype of donor Blood, December 1, 2005; 106(12): 3995 - 4001. [Abstract] [Full Text] [PDF]
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J. E. Foley, U. Jung, A. Miera, T. Borenstein, J. Mariotti, M. Eckhaus, B. E. Bierer, and D. H. Fowler Ex Vivo Rapamycin Generates Donor Th2 Cells That Potently Inhibit Graft-versus-Host Disease and Graft-versus-Tumor Effects via an IL-4-Dependent Mechanism J. Immunol., November 1, 2005; 175(9): 5732 - 5743. [Abstract] [Full Text] [PDF]
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P. Romagnoli, D. Hudrisier, and J. P. M. van Meerwijk Molecular Signature of Recent Thymic Selection Events on Effector and Regulatory CD4+ T Lymphocytes J. Immunol., November 1, 2005; 175(9): 5751 - 5758. [Abstract] [Full Text] [PDF]
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L. Li, W. R. Godfrey, S. B. Porter, Y. Ge, C. H. June, B. R. Blazar, and V. A. Boussiotis CD4+CD25+ regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy Blood, November 1, 2005; 106(9): 3068 - 3073. [Abstract] [Full Text] [PDF]
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C. A. Wysocki, Q. Jiang, A. Panoskaltsis-Mortari, P. A. Taylor, K. P. McKinnon, L. Su, B. R. Blazar, and J. S. Serody Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease Blood, November 1, 2005; 106(9): 3300 - 3307. [Abstract] [Full Text] [PDF]
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E. Zorn, H. T. Kim, S. J. Lee, B. H. Floyd, D. Litsa, S. Arumugarajah, R. Bellucci, E. P. Alyea, J. H. Antin, R. J. Soiffer, et al. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease Blood, October 15, 2005; 106(8): 2903 - 2911. [Abstract] [Full Text] [PDF]
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C. J. Funatake, N. B. Marshall, L. B. Steppan, D. V. Mourich, and N. I. Kerkvliet Cutting Edge: Activation of the Aryl Hydrocarbon Receptor by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Generates a Population of CD4+CD25+ Cells with Characteristics of Regulatory T Cells J. Immunol., October 1, 2005; 175(7): 4184 - 4188. [Abstract] [Full Text] [PDF]
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B. R Blazar and W. J Murphy Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD) Phil Trans R Soc B, September 29, 2005; 360(1461): 1747 - 1767. [Abstract] [Full Text] [PDF]
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M. Beyer, M. Kochanek, K. Darabi, A. Popov, M. Jensen, E. Endl, P. A. Knolle, R. K. Thomas, M. von Bergwelt-Baildon, S. Debey, et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine Blood, September 15, 2005; 106(6): 2018 - 2025. [Abstract] [Full Text] [PDF]
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D. J. Mekala, R. S. Alli, and T. L. Geiger IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T lymphocytes PNAS, August 16, 2005; 102(33): 11817 - 11822. [Abstract] [Full Text] [PDF]
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H. J. P. M. Koenen, E. Fasse, and I. Joosten CD27/CFSE-Based Ex Vivo Selection of Highly Suppressive Alloantigen-Specific Human Regulatory T Cells J. Immunol., June 15, 2005; 174(12): 7573 - 7583. [Abstract] [Full Text] [PDF]
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M. Battaglia, A. Stabilini, and M.-G. Roncarolo Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells Blood, June 15, 2005; 105(12): 4743 - 4748. [Abstract] [Full Text] [PDF]
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J. D. Carter, G. M. Calabrese, M. Naganuma, and U. Lorenz Deficiency of the Src Homology Region 2 Domain-Containing Phosphatase 1 (SHP-1) Causes Enrichment of CD4+CD25+ Regulatory T Cells J. Immunol., June 1, 2005; 174(11): 6627 - 6638. [Abstract] [Full Text] [PDF]
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J. G. Heuer, T. Zhang, J. Zhao, C. Ding, M. Cramer, K. L. Justen, S. L. Vonderfecht, and S. Na Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis J. Immunol., June 1, 2005; 174(11): 7141 - 7146. [Abstract] [Full Text] [PDF]
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S. J. Lee New approaches for preventing and treating chronic graft-versus-host disease Blood, June 1, 2005; 105(11): 4200 - 4206. [Abstract] [Full Text] [PDF]
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P. A. Taylor, A. Panoskaltsis-Mortari, G. J. Freeman, A. H. Sharpe, R. J. Noelle, A. Y. Rudensky, T. W. Mak, J. S. Serody, and B. R. Blazar Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM) Blood, April 15, 2005; 105(8): 3372 - 3380. [Abstract] [Full Text] [PDF]
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H. Gur, R. Krauthgamer, E. Bachar-Lustig, H. Katchman, R. Arbel-Goren, A. Berrebi, T. Klein, A. Nagler, A. Tabilio, M. F. Martelli, et al. Immune regulatory activity of CD34+ progenitor cells: evidence for a deletion-based mechanism mediated by TNF-{alpha} Blood, March 15, 2005; 105(6): 2585 - 2593. [Abstract] [Full Text] [PDF]
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D. J. Mekala and T. L. Geiger Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes Blood, March 1, 2005; 105(5): 2090 - 2092. [Abstract] [Full Text] [PDF]
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J. Ermann, P. Hoffmann, M. Edinger, S. Dutt, F. G. Blankenberg, J. P. Higgins, R. S. Negrin, C. G. Fathman, and S. Strober Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD Blood, March 1, 2005; 105(5): 2220 - 2226. [Abstract] [Full Text] [PDF]
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G. Lombardi CD4+CD25+ T cells, transplant engraftment, and allospecific tolerance Blood, February 15, 2005; 105(4): 1375 - 1376. [Full Text] [PDF]
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A. M. Hanash and R. B. Levy Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation Blood, February 15, 2005; 105(4): 1828 - 1836. [Abstract] [Full Text] [PDF]
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W. R. Godfrey, D. J. Spoden, Y. G. Ge, S. R. Baker, B. Liu, B. L. Levine, C. H. June, B. R. Blazar, and S. B. Porter Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function Blood, January 15, 2005; 105(2): 750 - 758. [Abstract] [Full Text] [PDF]
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C. T. Duthoit, D. J. Mekala, R. S. Alli, and T. L. Geiger Uncoupling of IL-2 Signaling from Cell Cycle Progression in Naive CD4+ T Cells by Regulatory CD4+CD25+ T Lymphocytes J. Immunol., January 1, 2005; 174(1): 155 - 163. [Abstract] [Full Text] [PDF]
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P. A. Taylor, A. Panoskaltsis-Mortari, J. M. Swedin, P. J. Lucas, R. E. Gress, B. L. Levine, C. H. June, J. S. Serody, and B. R. Blazar L-Selectinhi but not the L-selectinlo CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection Blood, December 1, 2004; 104(12): 3804 - 3812. [Abstract] [Full Text] [PDF]
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Y. L. Colson, K. Christopher, J. Glickman, K. N. Taylor, R. Wright, and D. L. Perkins Absence of clinical GVHD and the in vivo induction of regulatory T cells after transplantation of facilitating cells Blood, December 1, 2004; 104(12): 3829 - 3835. [Abstract] [Full Text] [PDF]
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 L. Zou, B. Barnett, H. Safah, V. F. LaRussa, M. Evdemon-Hogan, P. Mottram, S. Wei, O. David, T. J. Curiel, and W. Zou Bone Marrow Is a Reservoir for CD4+CD25+ Regulatory T Cells that Traffic through CXCL12/CXCR4 Signals Cancer Res., November 15, 2004; 64(22): 8451 - 8455. [Abstract] [Full Text] [PDF]
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E. A. Moseman, X. Liang, A. J. Dawson, A. Panoskaltsis-Mortari, A. M. Krieg, Y.-J. Liu, B. R. Blazar, and W. Chen Human Plasmacytoid Dendritic Cells Activated by CpG Oligodeoxynucleotides Induce the Generation of CD4+CD25+ Regulatory T Cells J. Immunol., October 1, 2004; 173(7): 4433 - 4442. [Abstract] [Full Text] [PDF]
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Y. Miura, C. J. Thoburn, E. C. Bright, M. L. Phelps, T. Shin, E. C. Matsui, W. H. Matsui, S. Arai, E. J. Fuchs, G. B. Vogelsang, et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease Blood, October 1, 2004; 104(7): 2187 - 2193. [Abstract] [Full Text] [PDF]
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K. V. Komanduri and R. E. Champlin GVHD therapy: the best-laid schemes... Blood, September 1, 2004; 104(5): 1240 - 1241. [Full Text] [PDF]
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B. E. Anderson, J. M. McNiff, C. Matte, I. Athanasiadis, W. D. Shlomchik, and M. J. Shlomchik Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease Blood, September 1, 2004; 104(5): 1565 - 1573. [Abstract] [Full Text] [PDF]
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G. Zheng, B. Wang, and A. Chen The 4-1BB Costimulation Augments the Proliferation of CD4+CD25+ Regulatory T Cells J. Immunol., August 15, 2004; 173(4): 2428 - 2434. [Abstract] [Full Text] [PDF]
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E. Nishimura, T. Sakihama, R. Setoguchi, K. Tanaka, and S. Sakaguchi Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells Int. Immunol., August 1, 2004; 16(8): 1189 - 1201. [Abstract] [Full Text] [PDF]
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P. Hoffmann, R. Eder, L. A. Kunz-Schughart, R. Andreesen, and M. Edinger Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells Blood, August 1, 2004; 104(3): 895 - 903. [Abstract] [Full Text] [PDF]
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W. R. Godfrey, Y. G. Ge, D. J. Spoden, B. L. Levine, C. H. June, B. R. Blazar, and S. B. Porter In vitro-expanded human CD4+CD25+ T-regulatory cells can markedly inhibit allogeneic dendritic cell-stimulated MLR cultures Blood, July 15, 2004; 104(2): 453 - 461. [Abstract] [Full Text] [PDF]
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L. Graca, A. Le Moine, C.-Y. Lin, P. J. Fairchild, S. P. Cobbold, and H. Waldmann Donor-specific transplantation tolerance: The paradoxical behavior of CD4+CD25+ T cells PNAS, July 6, 2004; 101(27): 10122 - 10126. [Abstract] [Full Text] [PDF]
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 Q. Tang, K. J. Henriksen, M. Bi, E. B. Finger, G. Szot, J. Ye, E. L. Masteller, H. McDevitt, M. Bonyhadi, and J. A. Bluestone In Vitro-expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes J. Exp. Med., June 7, 2004; 199(11): 1455 - 1465. [Abstract] [Full Text] [PDF]
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A. Fietta, F. Meloni, M. Stanzani, and K. V. Komanduri Only genuine CD4+CD25+ Tregs may be friends or foes Blood, June 1, 2004; 103(11): 4369 - 4370. [Full Text] [PDF]
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O. Joffre, N. Gorsse, P. Romagnoli, D. Hudrisier, and J. P. M. van Meerwijk Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes Blood, June 1, 2004; 103(11): 4216 - 4221. [Abstract] [Full Text] [PDF]
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F. J. Clark, R. Gregg, K. Piper, D. Dunnion, L. Freeman, M. Griffiths, G. Begum, P. Mahendra, C. Craddock, P. Moss, et al. Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells Blood, March 15, 2004; 103(6): 2410 - 2416. [Abstract] [Full Text] [PDF]
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B. J. Chen, X. Cui, G. D. Sempowski, C. Liu, and N. J. Chao Transfer of allogeneic CD62L- memory T cells without graft-versus-host disease Blood, February 15, 2004; 103(4): 1534 - 1541. [Abstract] [Full Text] [PDF]
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L. A. Stephens, A. N. Barclay, and D. Mason Phenotypic characterization of regulatory CD4+CD25+ T cells in rats Int. Immunol., February 1, 2004; 16(2): 365 - 375. [Abstract] [Full Text] [PDF]
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S. G. Zheng, J. H. Wang, M. N. Koss, F. Quismorio Jr., J. D. Gray, and D. A. Horwitz CD4+ and CD8+ Regulatory T Cells Generated Ex Vivo with IL-2 and TGF-{beta} Suppress a Stimulatory Graft-versus-Host Disease with a Lupus-Like Syndrome J. Immunol., February 1, 2004; 172(3): 1531 - 1539. [Abstract] [Full Text] [PDF]
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S. R. Solomon CD4+CD25+ T cells: friends or foes? Blood, February 1, 2004; 103(3): 757 - 757. [Full Text] [PDF]
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M. Stanzani, S. L. R. Martins, R. M. Saliba, L. S. St. John, S. Bryan, D. Couriel, J. McMannis, R. E. Champlin, J. J. Molldrem, and K. V. Komanduri CD25 expression on donor CD4+ or CD8+ T cells is associated with an increased risk for graft-versus-host disease after HLA-identical stem cell transplantation in humans Blood, February 1, 2004; 103(3): 1140 - 1146. [Abstract] [Full Text] [PDF]
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P. A. Taylor, C. J. Lees, S. Fournier, J. P. Allison, A. H. Sharpe, and B. R. Blazar B7 Expression on T Cells Down-Regulates Immune Responses through CTLA-4 Ligation via R-T Interactions J. Immunol., January 1, 2004; 172(1): 34 - 39. [Abstract] [Full Text] [PDF]
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H. J. P. M. Koenen, E. Fasse, and I. Joosten IL-15 and Cognate Antigen Successfully Expand De Novo-Induced Human Antigen-Specific Regulatory CD4+ T Cells That Require Antigen-Specific Activation for Suppression J. Immunol., December 15, 2003; 171(12): 6431 - 6441. [Abstract] [Full Text] [PDF]
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Abstract
Introduction
