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The Journal of Immunology, 2001, 167: 1137-1140.
Copyright © 2001 by The American Association of Immunologists

Cutting Edge

Cutting Edge: Control of CD8+ T Cell Activation by CD4+CD25+ Immunoregulatory Cells

Ciriaco A. Piccirillo and Ethan M. Shevach1

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results and Discussion
 References
 
CD4+CD25+ regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4+CD25- T cells and are potent suppressors of CD4+CD25- T cell activation in vitro. We demonstrate that CD4+CD25+ T cells also suppress both proliferation and IFN-{gamma} production by CD8+ T cells induced either by polyclonal or Ag-specific stimuli. CD4+CD25+ T cells inhibit the activation of CD8+ responders by inhibiting both IL-2 production and up-regulation of IL-2R{alpha}-chain (CD25) expression. Suppression is mediated via a T-T interaction as activated CD4+CD25+ T cells suppress the responses of TCR-transgenic CD8+ T cells stimulated with soluble peptide-MHC class I tetramers in the complete absence of APC. These results broaden the immunoregulatory role played by CD4+CD25+ T cells in the prevention of autoimmune diseases, but also raise the possibility that they may hinder the induction of effector CD8+ T cells to tumor or foreign Ags.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results and Discussion
 References
 
Studies in a number of experimental models have demonstrated the existence of regulatory T cell populations that prevent the activation of autoreactive T cells (1, 2, 3). The most useful marker to date for identification of regulatory T cells is the CD25 (IL-2R{alpha}-chain) Ag that is present on 5–10% of CD4+ T cells in normal animals (4, 5, 6, 7, 8). The functional properties of murine CD4+CD25+ T cells have been extensively studied in vitro. They demonstrate profound anergy to stimulation via their TCR, and this anergic state cannot be reversed by costimulation with anti-CD28 (9, 10). More importantly, when CD4+CD25+ T cells are cocultured with CD4+CD25- T cells, they induced profound suppression of T cell activation by down-regulating IL-2 production in the responding CD4+CD25- T cells (10). The suppressive activity of the CD4+CD25+ T cells requires that they be activated via their TCR and is cell contact dependent but cytokine independent (10, 11).

The mechanism by which CD4+CD25+ T cells mediate their suppressive effects is poorly understood. The physiologic ligand recognized by their TCR is unknown, and considerable controversy exists as to their cellular target. Thornton and Shevach (12) have demonstrated that the suppressors do not modulate APC function, whereas other laboratories have raised the possibility that they act by suppressing APC function (13) or by competing for APC-derived costimulatory signals (9). The potential suppressive activity of CD4+CD25+ T cells on non-CD4+ responder cells has not been studied in detail. Here, we demonstrate that CD4+CD25+ T cells suppress CD8+ T cell proliferation and IFN-{gamma} production induced by polyclonal or Ag-specific stimuli. In addition, the effects of the CD4+CD25+ T cells on CD8+ cells are more complex than their effects on CD4+CD25- responders, because they suppress both IL-2 production and CD25 expression. Finally, we made use of peptide-MHC tetramers to stimulate CD8+ responders in a two-cell suppressor assay system to formally demonstrate that CD4+CD25+ cells mediate their suppressor function via a T-T cell interaction and in the absence of APC.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results and Discussion
 References
 
Mice

Female C57BL/6 and BALB/c mice were obtained from the National Cancer Institute (Frederick, MD). OT-I (specific for OVA257–264 peptide), F5 (specific for nucleoprotein (NP)366–374 influenza peptide), and P14 (specific for lymphocytic choriomeningitis virus (LCMV) gp33–41 peptide) CD8+ TCR-transgenic (Tg) mice were obtained from Taconic Farms (Germantown, NY). All mice used were 6–12 wk of age.

The mAbs

The following Abs were used for flow cytometry experiments: biotin-anti-CD25 (7D4 clone), FITC-streptavidin, PE-anti-CD4, PE-anti-CD8, FITC-anti-CD25, FITC-anti-CD69, and purified anti-CD3{epsilon} (2C11), all of which were purchased from BD PharMingen (San Diego, CA).

Peptides

OT-I OVA257–264, F5 NP366–374, and LCMV gp33–41 peptides were provided by R. Germain and J. Yewdell (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD). Peptides were synthesized and purified by the Laboratory of Molecular Structure Peptide Synthesis Laboratory (National Institute of Allergy and Infectious Diseases, National Institutes of Health).

Tetramers

MHC class I H-2Kb-OVA257–264 tetramer solutions were prepared at the National Institute of Allergy and Infectious Diseases tetramer facility.

Cell purification and culture

CD4+CD25+ T cells were isolated on a FACStar cell sorter (BD Biosciences, San Jose, CA) as described previously (10). The purity of the final CD4+CD25+ preparation was typically >95%. T-depleted spleen cells (10; TdS) were irradiated at 3000 rad and pulsed for 30 min at 37°C with an appropriate peptide. Activated CD4+CD25+ cells were prepared as previously described (12). Briefly, cell-sorted CD4+CD25+ cells were cultured with irradiated APC (1:1 ratio), anti-CD3 (0.5 µg/ml), and human IL-2 (5 ng/ml, 100 U/ml) for 72 h and were then split and maintained in IL-2 medium for ~7–14 days. CD8+ T cells were purified either by negative (depletion of B220-, CD4-, and I-Ab-positive cells) or positive selection (using CD8{alpha} magnetic beads) on the AutoMACS magnetic separation system (Miltenyi Biotec, Auburn, CA). For experiments involving tetramer stimulation, OT-I CD8+ T cells were FACS purified using Abs against Thy1.2 and CD8{alpha} molecules, with final purities of >99%.

Proliferation assays

Proliferation assays were performed by culturing CD8+ T cells (5 x 104) in flat-bottom microtiter plates (0.2 ml) with peptide-pulsed APC (1–2 x 105) and resting or activated CD4+CD25+ or CD4+CD25- T cells for 72 h at 37°C in complete medium (10). Human rIL-2 was purchased from Peprotech (Rocky Hill, NJ). Cell cultures were pulsed with [3H]TdR for the last 8 h. All data represent the average cpm of triplicate determinations. All proliferation experiments were repeated at least three times.

For cytokine production, supernatants were taken at 72 h, and the production of IFN-{gamma} was measured using an ELISA kit (R&D Systems, Minneapolis, MN).

Flow cytometry

Cells were collected and stained with PE-CD8{alpha} and FITC-CD69 or FITC-CD25 and analyzed with a FACScan flow cytometer (BD Biosciences).


   Results and Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
References
 
When freshly explanted CD4+CD25+ T cells from normal mice were cocultured with F5 TCR-Tg CD8+ T cells, significant cell-dose-dependent suppression of proliferation was observed with soluble anti-CD3 as the stimulus in the presence of APC (Fig. 1GoA). When the TCR-Tg cells were stimulated with specific peptide, no inhibition of proliferation was observed (data not shown). When activated CD4+CD25+ T cells from normal mice were used, marked suppression of proliferation of F5 CD8+ TCR-Tg T cells was observed with peptide stimulation (Fig. 1GoC). This finding confirms previous studies (12) using CD4+ T cells as responders in which the CD4+CD25+ T cells required activation via their TCR to manifest suppressor function, but following activation, suppressor effector function was Ag-nonspecific and did not require restimulation of the suppressors via their TCR.



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  		FIGURE 1. CD4+CD25+ T cells suppress CD8+ T cell proliferation and effector function. Tg F5 CD8+ T cells (5 x 104) were stimulated with anti-CD3 and TdS (2 x 105; A and B) or NP366–374 peptide-pulsed TdS (2 x 105; C and D) and in the presence of either freshly isolated (A and B) or activated (C and D) CD4+CD25+ ({blacksquare}) or CD4+CD25- ({square}) T cells. Proliferation (A and C) and IFN-{gamma} production (B and D) were measured. Results from a representative experiment are shown.

 
Because CD8+ T cells will produce significant amounts of IFN-{gamma} in the absence of previous priming, we next studied the effects of CD4+CD25+ T cells on the capacity of CD8+ T cells to produce IFN-{gamma}. Freshly explanted CD4+CD25+ T cells readily suppressed IFN-{gamma} production by CD8+ T cells stimulated with anti-CD3 (Fig. 1GoB), and activated CD4+CD25+ T cells suppressed IFN-{gamma} production when the CD8+ T cells were stimulated with specific peptide (Fig. 1GoD). We have consistently shown >50% suppression of both proliferation and IFN-{gamma} secretion at a CD25+:CD8 ratio of 1:2, and >75% suppression at a 1:1 cell ratio. CD4+CD25+ T cells (Fig. 1Go, A and C) cultured alone do not proliferate and do not secrete IFN-{gamma} (data not shown). CD4+CD25- T cells (Fig. 1GoC) cultured in the absence of CD8+ T cells do not produce IFN-{gamma} (data not shown).

IL-2 will reverse suppression when CD4+CD25+ suppressors are cocultured with CD4+CD25- responders. It has been proposed that IL-2 can directly act on the suppressors and reverse their anergic phenotype and consequently disable their suppressive capability (14). Alternatively, the addition of exogenous IL-2 may simply be circumventing the block in IL-2 production induced in the responders by the CD4+CD25+ suppressors. When fresh CD4+CD25+ T cells (Fig. 2GoA) or activated CD4+CD25+ T cells (Fig. 2GoB) were cocultured with OT-I CD8+ T cells, significant suppression of proliferation (~60%) and IFN-{gamma} production (Fig. 2GoC) was observed with soluble anti-CD3 or peptide stimulation. Suppression was not reversed by the addition of exogenous IL-2 at all suppressor:responder ratios or by enhancement of endogenous IL-2 production by the addition of anti-CD28 (data not shown). Increasing the amount of IL-2 added to the cocultures to 100 U/ml also had no effect. It should be noted that the proliferative response of CD4+CD25+ T cells to IL-2 is modest when compared with activated CD4+CD25- T cells. Thus, the contribution of the activated CD4+CD25+ T cells to the proliferative responses in the cocultures performed in the presence of IL-2 is also minimal but may contribute some residual proliferation to the culture. The hypothesis (9) that IL-2 abrogates suppressor function is not supported by our studies on CD8+ responders because suppression is clearly maintained in the presence of IL-2.



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  		FIGURE 2. IL-2 does not reverse CD4+CD25+-mediated suppression. A, Tg OT-I CD8+ T cells (5 x 104) were stimulated with anti-CD3 (0.5 µg/ml) and TdS (2 x 105) and either freshly isolated CD4+CD25+ (circles) or CD4+CD25- (squares) T cells in the presence (filled symbols) or absence (open symbols) of exogenous IL-2 (100 U/ml). B, Tg OT-I CD8+ T cells (5 x 104) were stimulated with OVA257–264 peptide-pulsed TdS (2 x 105) and either activated CD4+CD25+ (circles) or CD4+CD25- (squares) T cells in the presence (filled symbols) or absence (open symbols) of exogenous IL-2 (100 U/ml). Proliferation was assayed as in Fig. 1GoC. Supernatants from B were collected at 72 h, and IFN-{gamma} ELISA was performed.

 
We next examined the expression of CD25 on F5 CD8+ T cells stimulated either in the presence or absence of CD4+CD25+ T cells. Following 6 h of stimulation with peptide-pulsed APC, up-regulation of CD25 expression on the F5 CD8+ T cell responders was similar in presence or absence of CD4+CD25+ T cells (Fig. 3GoA). However, no further up-regulation of CD25 on the CD8+ responders was seen in the CD4+CD25+/CD8+ cocultures (Fig. 3GoA). The expression of CD69 was identical on CD8+ responders stimulated in the presence or absence of CD4+CD25+ cells at both time points tested (Fig. 3GoA). In multiple (n = 5) experiments, addition of activated CD4+CD25+ T cells resulted in 73 ± 5% suppression of the induction of CD25 when the responding CD8+ T cells were assayed for CD25 expression following 24 h of stimulation. The addition of exogenous IL-2 (100 U/ml) also failed to restore the level of CD25 expression on suppressed responders to levels seen on responders cultured alone (Fig. 3GoB) or responders cultured with activated CD4+CD25- T cells (data not shown).



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  		FIGURE 3. CD4+CD25+ regulatory T cells suppress IL-2R{alpha} expression on responding CD8+ T cells, and IL-2 fails to rescue its expression. A, Tg F5 CD8+ T cells (5 x 105) were stimulated with NP366–374 peptide-pulsed TdS (2 x 106) either alone (filled line) or with activated CD4+CD25+ T cells (5 x 105; solid line). FACS analysis for CD25 and CD69 was performed at 6 and 24 h and compared with unstimulated CD8+ T cells (dotted line). B, Tg P14 CD8+ T cells (5 x 105) were stimulated with LCMV gp33–41 peptide-pulsed TdS (2 x 106) either alone (solid line) or with activated CD4+CD25+ T cells (5 x 105; dotted line) in the presence of exogenous IL-2 (100 U/ml). FACS analysis for CD25 was performed at 24 h and compared with unstimulated CD8+ T cells (filled line). All histograms were gated on CD8+ T cells. CD8+ T cells stimulated in the presence of activated CD4+CD25- cells displayed CD25 and CD69 expression levels indistinguishable to those observed when CD8+ T cells were cultured alone (data not shown).

 
Soluble tetramer stimulation of OT-I CD8+ T cells resulted in robust T cell proliferation (Fig. 4GoA) and IFN-{gamma} production (Fig. 4GoB), confirming previous studies (15, 16, 17) showing that CD8+ T cells can be efficiently activated in the absence of APC and APC-derived costimulatory signals. CD8+ T cells from normal C57BL/6 mice did not proliferate at any tetramer concentration (Fig. 4GoA), nor did an irrelevant soluble tetramer (H-2Db/CEA antigenic peptide) preparation induce proliferation (data not shown) or IFN-{gamma} production (Fig. 4GoB). To directly assess whether CD4+CD25+ T cells suppress CD8+ T cell responders by modulating APC function or by direct T-T contact, we stimulated highly purified OT-I CD8+ T cells (>99% pure) with soluble MHC I H-2Kb-OVA257–264 tetramers, in the presence or absence of titrated numbers of CD4+CD25+ T cells. Marked suppression of both proliferation and IFN-{gamma} production was seen in the presence of CD4+CD25+ T cells, but not CD4+CD25- cells, even at low CD4+CD25+:CD8+ ratios (Fig. 4Go, C and D). Taken together, the results from this two-cell system conclusively demonstrate that CD4+CD25+-mediated suppression occurs via a T-T cell interaction, and the APC is not directly required for the delivery of the suppressive signal to responding CD8+ T cells.



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  		FIGURE 4. Suppression mediated by CD4+CD25+ T cells is APC-independent. A, Tg (OT-I) and non-Tg (wild-type B6) CD8+ T cells (5 x 104) were stimulated with varying concentrations of soluble MHC I H-2Kb-OVA257–264 tetramers. Proliferation was measured as in Fig. 1Go. B, Culture supernatants were harvested at 48 h, and IFN-{gamma} ELISA was performed. C, Tg OT-I CD8+ T cells (5 x 104) were stimulated with soluble MHC I H-2Kb-OVA257–264 tetramers (0.5 µg/ml) and titrated numbers of activated CD4+CD25+ ({blacksquare}) or CD4+CD25- ({square}) T cells, and proliferation was assayed. D, Supernatants were collected at 72 h, and IFN-{gamma} ELISA was performed.

 
CD8+ T cells may contribute to the immunopathogenesis of many autoimmune diseases (18, 19, 20, 21). Therefore, it is desirable that regulatory T cells be able to control autoreactive CD8+ T cells as well as CD4+ T cells. Most of the effects of regulatory CD4+CD25+ T cells on CD8+ responders were similar to those seen with CD4+ responders. However, several important differences should be noted. First, in addition to T cell proliferation, the capacity of fresh CD8+ T cells to manifest effector function such as the production of IFN-{gamma} was also suppressed. Second, whereas CD4+CD25+ T cells inhibit the activation of CD4+ responders by primarily blocking IL-2 production, CD4+CD25+ T cells regulate CD8+ T cell responses both by blocking IL-2 production as well as by lowering responsiveness to exogenous IL-2 and thereby potentially disrupting CD4 help for CD8+ T cells. Finally, CD4+CD25+ T cells can inhibit T cell activation by directly acting on responder CD8+ T cells in the absence of APC. However, this result does not exclude the possibility that CD4+CD25+ T cells might also exert inhibitory/deactivating effects on APC or use the APC surface as a platform on which the suppressor cells physically interact with CD4+ or CD8+ effectors in vivo.

Although immunoregulatory CD4+CD25+ cells function beneficially in vivo to protect the host against the development of autoimmunity, they may simultaneously prevent the host from mounting an immune response to autoantigens such as tumor Ags. Because IL-2 responsiveness by CD8+ T cells is a critical factor for cytokine production (IFN-{gamma}) and cytolytic activity (22, 23), our demonstration that CD4+CD25+ T cells down-regulate both IL-2 production and CD25 expression on CD8+ T cells may represent a significant impediment to the use of tumor or viral vaccines. Indeed, deletion of CD4+CD25+ T cells before the use of such vaccines may be needed for optimal immunotherapy.


   Footnotes
 
1 Address correspondence and reprint requests to Dr. Ethan M. Shevach, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive, Bethesda, Maryland 20892-1892. E-mail address: ems1{at}mail.nih.gov Back

2 Abbreviations used in this paper: NP, nucleoprotein; LCMV, lymphocytic choriomeningitis virus; Tg, transgenic; TdS, T-depleted spleen cells. Back

Received for publication April 30, 2001. Accepted for publication June 4, 2001.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 References
 

  1. Shevach, E. M.. 2000. Suppressor T cells: rebirth, function and homeostasis. Curr. Biol. 10:R572.[Medline]
  2. Fowell, D., D. Mason. 1993. Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes: characterization of the CD4+ T cell subset that inhibits this autoimmune potential. J. Exp. Med. 177:627.[Abstract/Free Full Text]
  3. Sakaguchi, S.. 2000. Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101:455.[Medline]
  4. Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, M. Toda. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor {alpha}-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155:1151.[Abstract]
  5. Powrie, F., M. W. Leach, S. Mauze, L. B. Caddle, R. L. Coffman. 1993. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int. Immunol. 5:1461.[Abstract/Free Full Text]
  6. Sakaguchi, S., M. Toda, M. Asano, M. Itoh, S. S. Morse, N. Sakaguchi. 1996. T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases. J. Autoimmun. 9:211.[Medline]
  7. Asano, M., M. Toda, N. Sakaguchi, S. Sakaguchi. 1996. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med. 184:387.[Abstract/Free Full Text]
  8. Salomon, B., D. J. Lenschow, L. Rhee, N. Ashourian, B. Singh, A. Sharpe, J. A. Bluestone. 2000. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12:431.[Medline]
  9. Takahashi, T., Y. Kuniyasu, M. Toda, N. Sakaguchi, M. Itoh, M. Iwata, J. Shimizu, S. Sakaguchi. 1998. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10:1969.[Abstract/Free Full Text]
  10. Thornton, A. M., E. M. Shevach. 1998. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188:287.[Abstract/Free Full Text]
  11. Takahashi, T., T. Tagami, S. Yamazaki, T. Uede, J. Shimizu, N. Sakaguchi, T. W. Mak, S. Sakaguchi. 2000. Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 192:303.[Abstract/Free Full Text]
  12. Thornton, A. M., E. M. Shevach. 2000. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol. 164:183.[Abstract/Free Full Text]
  13. Cederbom, L., H. Hall, F. Ivars. 2000. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur. J. Immunol. 30:1538.[Medline]
  14. Itoh, M., T. Takahashi, N. Sakaguchi, Y. Kuniyasu, J. Shimizu, F. Otsuka, S. Sakaguchi. 1999. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162:5317.[Abstract/Free Full Text]
  15. Wang, B., R. Maile, R. Greenwood, E. J. Collins, J. A. Frelinger. 2000. Naive CD8+ T cells do not require costimulation for proliferation and differentiation into cytotoxic effector cells. J. Immunol. 164:1216.[Abstract/Free Full Text]
  16. Lu, P., Y. L. Wang, P. S. Linsley. 1997. Regulation of self-tolerance by CD80/CD86 interactions. Curr. Opin. Immunol. 9:858.[Medline]
  17. Sepulveda, H., A. Cerwenka, T. Morgan, R. W. Dutton. 1999. CD28, IL-2-independent costimulatory pathways for CD8 T lymphocyte activation. J. Immunol. 163:1133.[Abstract/Free Full Text]
  18. Vizler, C., N. Bercovici, A. Cornet, C. Cambouris, R. S. Liblau. 1999. Role of autoreactive CD8+ T cells in organ-specific autoimmune diseases: insight from transgenic mouse models. Immunol. Rev. 169:81.[Medline]
  19. Herrera, P. L., D. M. Harlan, P. Vassalli. 2000. A mouse CD8 T cell-mediated acute autoimmune diabetes independent of the perforin and Fas cytotoxic pathways: possible role of membrane TNF. Proc. Natl. Acad. Sci. USA 97:279.[Abstract/Free Full Text]
  20. Wong, F. S., I. Visintin, L. Wen, R. A. Flavell, C. A. Janeway. 1996. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. J. Exp. Med. 183:67.[Abstract/Free Full Text]
  21. Wong, F. S., C. A. Janeway. 1997. The role of CD4 and CD8 T cells in type I diabetes in the NOD mouse. Res. Immunol. 148:327.[Medline]
  22. Sad, S., L. Krishnan. 1999. Cytokine deprivation of naive CD8+ T cells promotes minimal cell cycling but maximal cytokine synthesis and autonomous proliferation subsequently: a mechanism of self-regulation. J. Immunol. 163:2443.[Abstract/Free Full Text]
  23. Mosmann, T. R., S. Sad, L. Krishnan, T. G. Wegmann, L. J. Guilbert, M. Belosevic. 1995. Differentiation of subsets of CD4+ and CD8+ T cells. Ciba Found. Symp. 195:42.[Medline]



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M. A. Morse, A. C. Hobeika, T. Osada, D. Serra, D. Niedzwiecki, H. K. Lyerly, and T. M. Clay
Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines
Blood, August 1, 2008; 112(3): 610 - 618.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. D. Gritzapis, I. F. Voutsas, E. Lekka, N. Tsavaris, I. Missitzis, P. Sotiropoulou, S. Perez, M. Papamichail, and C. N. Baxevanis
Identification of a Novel Immunogenic HLA-A*0201-Binding Epitope of HER-2/neu with Potent Antitumor Properties
J. Immunol., July 1, 2008; 181(1): 146 - 154.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Vasir, Z. Wu, K. Crawford, J. Rosenblatt, C. Zarwan, A. Bissonnette, D. Kufe, and D. Avigan
Fusions of Dendritic Cells with Breast Carcinoma Stimulate the Expansion of Regulatory T Cells while Concomitant Exposure to IL-12, CpG Oligodeoxynucleotides, and Anti-CD3/CD28 Promotes the Expansion of Activated Tumor Reactive Cells
J. Immunol., July 1, 2008; 181(1): 808 - 821.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Serada, M. Fujimoto, M. Mihara, N. Koike, Y. Ohsugi, S. Nomura, H. Yoshida, T. Nishikawa, F. Terabe, T. Ohkawara, et al.
IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis
PNAS, July 1, 2008; 105(26): 9041 - 9046.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Poitrasson-Riviere, B. Bienvenu, A. Le Campion, C. Becourt, B. Martin, and B. Lucas
Regulatory CD4+ T Cells Are Crucial for Preventing CD8+ T Cell-Mediated Autoimmunity
J. Immunol., June 1, 2008; 180(11): 7294 - 7304.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. J. Winstead, J. M. Fraser, and A. Khoruts
Regulatory CD4+CD25+Foxp3+ T Cells Selectively Inhibit the Spontaneous Form of Lymphopenia-Induced Proliferation of Naive T Cells
J. Immunol., June 1, 2008; 180(11): 7305 - 7317.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Terme, N. Chaput, B. Combadiere, A. Ma, T. Ohteki, and L. Zitvogel
Regulatory T Cells Control Dendritic Cell/NK Cell Cross-Talk in Lymph Nodes at the Steady State by Inhibiting CD4+ Self-Reactive T Cells
J. Immunol., April 1, 2008; 180(7): 4679 - 4686.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. A. Fernandez, F. K. Puttur, Y. M. Wang, W. Howden, S. I. Alexander, and C. A. Jones
T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice
J. Immunol., February 1, 2008; 180(3): 1556 - 1564.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. M. Tiemessen, A. L. Jagger, H. G. Evans, M. J. C. van Herwijnen, S. John, and L. S. Taams
CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages
PNAS, December 4, 2007; 104(49): 19446 - 19451.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Ribot, G. Enault, S. Pilipenko, A. Huchenq, M. Calise, D. Hudrisier, P. Romagnoli, and J. P. M. van Meerwijk
Shaping of the Autoreactive Regulatory T Cell Repertoire by Thymic Cortical Positive Selection
J. Immunol., November 15, 2007; 179(10): 6741 - 6748.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Chaput, G. Darrasse-Jeze, A.-S. Bergot, C. Cordier, S. Ngo-Abdalla, D. Klatzmann, and O. Azogui
Regulatory T Cells Prevent CD8 T Cell Maturation by Inhibiting CD4 Th Cells at Tumor Sites
J. Immunol., October 15, 2007; 179(8): 4969 - 4978.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Giroux, E. Yurchenko, J. St.-Pierre, C. A. Piccirillo, and C. Perreault
T Regulatory Cells Control Numbers of NK Cells and CD8{alpha}+ Immature Dendritic Cells in the Lymph Node Paracortex
J. Immunol., October 1, 2007; 179(7): 4492 - 4502.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
J. M. M. den Haan, G. Kraal, and M. J. Bevan
Cutting Edge: Lipopolysaccharide Induces IL-10-Producing Regulatory CD4+ T Cells That Suppress the CD8+ T Cell Response
J. Immunol., May 1, 2007; 178(9): 5429 - 5433.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
J. Andersson, I. Stefanova, G. L. Stephens, and E. M. Shevach
CD4+CD25+ regulatory T cells are activated in vivo by recognition of self
Int. Immunol., April 1, 2007; 19(4): 557 - 566.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. Kotner and R. Tarleton
Endogenous CD4+ CD25+ Regulatory T Cells Have a Limited Role in the Control of Trypanosoma cruzi Infection in Mice
Infect. Immun., February 1, 2007; 75(2): 861 - 869.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. d. l. L. Garcia-Hernandez, A. Gray, B. Hubby, and W. M. Kast
In vivo Effects of Vaccination with Six-Transmembrane Epithelial Antigen of the Prostate: A Candidate Antigen for Treating Prostate Cancer
Cancer Res., February 1, 2007; 67(3): 1344 - 1351.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Joetham, K. Takada, C. Taube, N. Miyahara, S. Matsubara, T. Koya, Y.-H. Rha, A. Dakhama, and E. W. Gelfand
Naturally Occurring Lung CD4+CD25+ T Cell Regulation of Airway Allergic Responses Depends on IL-10 Induction of TGF-beta
J. Immunol., February 1, 2007; 178(3): 1433 - 1442.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. Peluso, M. C. Fantini, D. Fina, R. Caruso, M. Boirivant, T. T. MacDonald, F. Pallone, and G. Monteleone
IL-21 Counteracts the Regulatory T Cell-Mediated Suppression of Human CD4+ T Lymphocytes
J. Immunol., January 15, 2007; 178(2): 732 - 739.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
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]

Home page
 Cancer Res.Home page
M. Kurooka and Y. Kaneda
Inactivated Sendai Virus Particles Eradicate Tumors by Inducing Immune Responses through Blocking Regulatory T Cells
Cancer Res., January 1, 2007; 67(1): 227 - 236.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Sharma, A. L. Dominguez, and J. Lustgarten
High Accumulation of T Regulatory Cells Prevents the Activation of Immune Responses in Aged Animals
J. Immunol., December 15, 2006; 177(12): 8348 - 8355.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. J. Dobrzanski, J. B. Reome, J. C. Hylind, and K. A. Rewers-Felkins
CD8-Mediated Type 1 Antitumor Responses Selectively Modulate Endogenous Differentiated and Nondifferentiated T Cell Localization, Activation, and Function in Progressive Breast Cancer
J. Immunol., December 1, 2006; 177(11): 8191 - 8201.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. W. Cunningham
T Regulatory Cells: Sentinels Against Autoimmune Heart Disease
Circ. Res., November 10, 2006; 99(10): 1024 - 1026.
[Full Text] [PDF]

Home page
 BloodHome page
J. Carreras, A. Lopez-Guillermo, B. C. Fox, L. Colomo, A. Martinez, G. Roncador, E. Montserrat, E. Campo, and A. H. Banham
High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma
Blood, November 1, 2006; 108(9): 2957 - 2964.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. J. Lucas, S.-J. Kim, C. L. Mackall, W. G. Telford, Y.-W. Chu, F. T. Hakim, and R. E. Gress
Dysregulation of IL-15-mediated T-cell homeostasis in TGF-beta dominant-negative receptor transgenic mice
Blood, October 15, 2006; 108(8): 2789 - 2795.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Gasper-Smith, I. Marriott, and K. L. Bost
Murine {gamma}-Herpesvirus 68 Limits Naturally Occurring CD4+CD25+ T Regulatory Cell Activity following Infection
J. Immunol., October 1, 2006; 177(7): 4670 - 4678.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D.-A. Gross, P. Chappert, M. Leboeuf, V. Monteilhet, L. Van Wittenberghe, O. Danos, and J. Davoust
Simple conditioning with monospecific CD4+CD25+ regulatory T cells for bone marrow engraftment and tolerance to multiple gene products
Blood, September 15, 2006; 108(6): 1841 - 1848.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Toda and C. A. Piccirillo
Development and function of naturally occurring CD4+CD25+ regulatory T cells
J. Leukoc. Biol., September 1, 2006; 80(3): 458 - 470.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Oida, L. Xu, H. L. Weiner, A. Kitani, and W. Strober
TGF-beta-Mediated Suppression by CD4+CD25+ T Cells Is Facilitated by CTLA-4 Signaling
J. Immunol., August 15, 2006; 177(4): 2331 - 2339.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. W. Lim, H. E. Broxmeyer, and C. H. Kim
Regulation of Trafficking Receptor Expression in Human Forkhead Box P3+ Regulatory T Cells
J. Immunol., July 15, 2006; 177(2): 840 - 851.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
H. Inaba and T. L. Geiger
Defective cell cycle induction by IL-2 in naive T-cells antigen stimulated in the presence of refractory T-lymphocytes
Int. Immunol., July 1, 2006; 18(7): 1043 - 1054.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Manigold, E.-C. Shin, E. Mizukoshi, K. Mihalik, K. K. Murthy, C. M. Rice, C. A. Piccirillo, and B. Rehermann
Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C
Blood, June 1, 2006; 107(11): 4424 - 4432.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Nishikawa, F. Qian, T. Tsuji, G. Ritter, L. J. Old, S. Gnjatic, and K. Odunsi
Influence of CD4+CD25+ Regulatory T Cells on Low/High-Avidity CD4+ T Cells following Peptide Vaccination
J. Immunol., May 15, 2006; 176(10): 6340 - 6346.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D.-M. Zhao, A. M. Thornton, R. J. DiPaolo, and E. M. Shevach
Activated CD4+CD25+ T cells selectively kill B lymphocytes
Blood, May 15, 2006; 107(10): 3925 - 3932.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Houot, I. Perrot, E. Garcia, I. Durand, and S. Lebecque
Human CD4+CD25high Regulatory T Cells Modulate Myeloid but Not Plasmacytoid Dendritic Cells Activation
J. Immunol., May 1, 2006; 176(9): 5293 - 5298.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Wuthrich, P. L. Fisette, H. I. Filutowicz, and B. S. Klein
Differential Requirements of T Cell Subsets for CD40 Costimulation in Immunity to Blastomyces dermatitidis
J. Immunol., May 1, 2006; 176(9): 5538 - 5547.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. Barao, A. M. Hanash, W. Hallett, L. A. Welniak, K. Sun, D. Redelman, B. R. Blazar, R. B. Levy, and W. J. Murphy
Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells
PNAS, April 4, 2006; 103(14): 5460 - 5465.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. E. Fecci, D. A. Mitchell, J. F. Whitesides, W. Xie, A. H. Friedman, G. E. Archer, J. E. Herndon II, D. D. Bigner, G. Dranoff, and J. H. Sampson
Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.
Cancer Res., March 15, 2006; 66(6): 3294 - 3302.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. J. Robertson, R. J. Messer, A. B. Carmody, and K. J. Hasenkrug
In Vitro Suppression of CD8+ T Cell Function by Friend Virus-Induced Regulatory T Cells
J. Immunol., March 15, 2006; 176(6): 3342 - 3349.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Lepage and R. Lapointe
Melanosomal Targeting Sequences from gp100 Are Essential for MHC Class II-Restricted Endogenous Epitope Presentation and Mobilization to Endosomal Compartments
Cancer Res., February 15, 2006; 66(4): 2423 - 2432.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Ghoreishi and J. P. Dutz
Tolerance Induction by Transcutaneous Immunization through Ultraviolet-Irradiated Skin Is Transferable through CD4+CD25+ T Regulatory Cells and Is Dependent on Host-Derived IL-10
J. Immunol., February 15, 2006; 176(4): 2635 - 2644.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S. G. Zheng, L. Meng, J. H. Wang, M. Watanabe, M. L. Barr, D. V. Cramer, J. D. Gray, and D. A. Horwitz
Transfer of regulatory T cells generated ex vivo modifies graft rejection through induction of tolerogenic CD4+CD25+ cells in the recipient
Int. Immunol., February 1, 2006; 18(2): 279 - 289.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Chattopadhyay, S. Mehrotra, A. Chhabra, U. Hegde, B. Mukherji, and N. G. Chakraborty
Effect of CD4+CD25+ and CD4+CD25- T Regulatory Cells on the Generation of Cytolytic T Cell Response to a Self but Human Tumor-Associated Epitope In Vitro
J. Immunol., January 15, 2006; 176(2): 984 - 990.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. K. Crellin, R. V. Garcia, O. Hadisfar, S. E. Allan, T. S. Steiner, and M. K. Levings
Human CD4+ T Cells Express TLR5 and Its Ligand Flagellin Enhances the Suppressive Capacity and Expression of FOXP3 in CD4+CD25+ T Regulatory Cells
J. Immunol., December 15, 2005; 175(12): 8051 - 8059.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. K. Asiedu, K. J. Goodwin, G. Balgansuren, S. M. Jenkins, S. Le Bas-Bernardet, U. Jargal, D. M. Neville Jr, and J. M. Thomas
Elevated T Regulatory Cells in Long-Term Stable Transplant Tolerance in Rhesus Macaques Induced by Anti-CD3 Immunotoxin and Deoxyspergualin
J. Immunol., December 15, 2005; 175(12): 8060 - 8068.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Brinster and E. M. Shevach
Bone Marrow-Derived Dendritic Cells Reverse the Anergic State of CD4+CD25+ T Cells without Reversing Their Suppressive Function
J. Immunol., December 1, 2005; 175(11): 7332 - 7340.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. A. Laheru, D. M. Pardoll, and E. M. Jaffee
Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology
Mol. Cancer Ther., November 1, 2005; 4(11): 1645 - 1652.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
F. Ghiringhelli, C. Menard, M. Terme, C. Flament, J. Taieb, N. Chaput, P. E. Puig, S. Novault, B. Escudier, E. Vivier, et al.
CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-{beta}-dependent manner
J. Exp. Med., October 17, 2005; 202(8): 1075 - 1085.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Mallone, S. A. Kochik, H. Reijonen, B. Carson, S. F. Ziegler, W. W. Kwok, and G. T. Nepom
Functional avidity directs T-cell fate in autoreactive CD4+ T cells
Blood, October 15, 2005; 106(8): 2798 - 2805.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
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]

Home page
 Infect. Immun.Home page
T. Voza, A. M. Vigario, E. Belnoue, A. C. Gruner, J.-C. Deschemin, M. Kayibanda, F. Delmas, C. J. Janse, B. Franke-Fayard, A. P. Waters, et al.
Species-Specific Inhibition of Cerebral Malaria in Mice Coinfected with Plasmodium spp.
Infect. Immun., August 1, 2005; 73(8): 4777 - 4786.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Bienvenu, B. Martin, C. Auffray, C. Cordier, C. Becourt, and B. Lucas
Peripheral CD8+CD25+ T Lymphocytes from MHC Class II-Deficient Mice Exhibit Regulatory Activity
J. Immunol., July 1, 2005; 175(1): 246 - 253.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
T. Boettler, H. C. Spangenberg, C. Neumann-Haefelin, E. Panther, S. Urbani, C. Ferrari, H. E. Blum, F. von Weizsacker, and R. Thimme
T Cells with a CD4+CD25+ Regulatory Phenotype Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Chronic Hepatitis C Virus Infection
J. Virol., June 15, 2005; 79(12): 7860 - 7867.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Kudo-Saito, J. Schlom, K. Camphausen, C. N. Coleman, and J. W. Hodge
The Requirement of Multimodal Therapy (Vaccine, Local Tumor Radiation, and Reduction of Suppressor Cells) to Eliminate Established Tumors
Clin. Cancer Res., June 15, 2005; 11(12): 4533 - 4544.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Karim, G. Feng, K. J. Wood, and A. R. Bushell
CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation
Blood, June 15, 2005; 105(12): 4871 - 4877.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Kojima, Y. Kanno, H. Hase, and T. Kobata
CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation
J. Immunol., May 15, 2005; 174(10): 5959 - 5967.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
D. Lundsgaard, T. L. Holm, L. Hornum, and H. Markholst
In Vivo Control of Diabetogenic T-Cells by Regulatory CD4+CD25+ T-Cells Expressing Foxp3
Diabetes, April 1, 2005; 54(4): 1040 - 1047.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
O. Franzese, P. T. F. Kennedy, A. J. Gehring, J. Gotto, R. Williams, M. K. Maini, and A. Bertoletti
Modulation of the CD8+-T-Cell Response by CD4+ CD25+ Regulatory T Cells in Patients with Hepatitis B Virus Infection
J. Virol., March 15, 2005; 79(6): 3322 - 3328.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. A. Ormandy, T. Hillemann, H. Wedemeyer, M. P. Manns, T. F. Greten, and F. Korangy
Increased Populations of Regulatory T Cells in Peripheral Blood of Patients with Hepatocellular Carcinoma
Cancer Res., March 15, 2005; 65(6): 2457 - 2464.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Zhou, S. J. Balin, M. Mashayekhi, K. W. Hwang, D. A. Palucki, and M.-L. Alegre
Transplantation Tolerance in NF-{kappa}B-Impaired Mice Is Not Due to Regulation but Is Prevented by Transgenic Expression of Bcl-xL
J. Immunol., March 15, 2005; 174(6): 3447 - 3453.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. A. Antony, C. A. Piccirillo, A. Akpinarli, S. E. Finkelstein, P. J. Speiss, D. R. Surman, D. C. Palmer, C.-C. Chan, C. A. Klebanoff, W. W. Overwijk, et al.
CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells
J. Immunol., March 1, 2005; 174(5): 2591 - 2601.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Alvaro, M. Lejeune, M. T. Salvado, R. Bosch, J. F. Garcia, J. Jaen, A. H. Banham, G. Roncador, C. Montalban, and M. A. Piris
Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T Cells
Clin. Cancer Res., February 15, 2005; 11(4): 1467 - 1473.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. E. Rao, A. L. Petrone, and P. D. Ponath
Differentiation and Expansion of T Cells with Regulatory Function from Human Peripheral Lymphocytes by Stimulation in the Presence of TGF-{beta}
J. Immunol., February 1, 2005; 174(3): 1446 - 1455.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M.-L. Chen, M. J. Pittet, L. Gorelik, R. A. Flavell, R. Weissleder, H. von Boehmer, and K. Khazaie
Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-{beta} signals in vivo
PNAS, January 11, 2005; 102(2): 419 - 424.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. Lindley, C. M. Dayan, A. Bishop, B. O. Roep, M. Peakman, and T. I.M. Tree
Defective Suppressor Function in CD4+CD25+ T-Cells From Patients With Type 1 Diabetes
Diabetes, January 1, 2005; 54(1): 92 - 99.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Weiss, V. Donkova-Petrini, L. Caccavelli, M. Balbo, C. Carbonneil, and Y. Levy
Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients
Blood, November 15, 2004; 104(10): 3249 - 3256.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Belnoue, C. Guettier, M. Kayibanda, S. Le Rond, A.-M. Crain-Denoyelle, C. Marchiol, M. Ziol, D. Fradelizi, L. Renia, and M. Viguier
Regression of Established Liver Tumor Induced by Monoepitopic Peptide-Based Immunotherapy
J. Immunol., October 15, 2004; 173(8): 4882 - 4888.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. L. Stephens, R. S. McHugh, M. J. Whitters, D. A. Young, D. Luxenberg, B. M. Carreno, M. Collins, and E. M. Shevach
Engagement of Glucocorticoid-Induced TNFR Family-Related Receptor on Effector T Cells by its Ligand Mediates Resistance to Suppression by CD4+CD25+ T Cells
J. Immunol., October 15, 2004; 173(8): 5008 - 5020.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. Liu and L. Lefrancois
Intestinal Epithelial Antigen Induces Mucosal CD8 T Cell Tolerance, Activation, and Inflammatory Response
J. Immunol., October 1, 2004; 173(7): 4324 - 4330.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
A. L. Kinter, M. Hennessey, A. Bell, S. Kern, Y. Lin, M. Daucher, M. Planta, M. McGlaughlin, R. Jackson, S. F. Ziegler, et al.
CD25+CD4+ Regulatory T Cells from the Peripheral Blood of Asymptomatic HIV-infected Individuals Regulate CD4+ and CD8+ HIV-specific T Cell Immune Responses In Vitro and Are Associated with Favorable Clinical Markers of Disease Status
J. Exp. Med., August 2, 2004; 200(3): 331 - 343.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
P. W Denton, C. M Tello, and R. W Melvold
CD8 + T cells reduce in vitro interferon-g production in Theiler's murine encephalomyelitis virus-induced demyelinating disease model
Multiple Sclerosis, August 1, 2004; 10(4): 370 - 375.
[Abstract] [PDF]

Home page
 J. Immunol.Home page
E. A. Wohlfert, M. K. Callahan, and R. B. Clark
Resistance to CD4+CD25+ Regulatory T Cells and TGF-{beta} in Cbl-b-/- Mice
J. Immunol., July 15, 2004; 173(2): 1059 - 1065.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
P. M. Stuart, B. Summers, J. E. Morris, L. A. Morrison, and D. A. Leib
CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1
J. Gen. Virol., July 1, 2004; 85(7): 2055 - 2063.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Stassen, H. Jonuleit, C. Muller, M. Klein, C. Richter, T. Bopp, S. Schmitt, and E. Schmitt
Differential Regulatory Capacity of CD25+ T Regulatory Cells and Preactivated CD25+ T Regulatory Cells on Development, Functional Activation, and Proliferation of Th2 Cells
J. Immunol., July 1, 2004; 173(1): 267 - 274.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Vigouroux, E. Yvon, E. Biagi, and M. K. Brenner
Antigen-induced regulatory T cells
Blood, July 1, 2004; 104(1): 26 - 33.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Mamura, W. Lee, T. J. Sullivan, A. Felici, A. L. Sowers, J. P. Allison, and J. J. Letterio
CD28 disruption exacerbates inflammation in Tgf-{beta}1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-{beta}1
Blood, June 15, 2004; 103(12): 4594 - 4601.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. L. Sumpter and D. S. Wilkes
Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection
Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1129 - L1139.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. A. Lyman, S. Aung, J. A. Biggs, and L. A. Sherman
A Spontaneously Arising Pancreatic Tumor Does Not Promote the Differentiation of Naive CD8+ T Lymphocytes into Effector CTL
J. Immunol., June 1, 2004; 172(11): 6558 - 6567.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
B. K. Choi, J. S. Bae, E. M. Choi, W. J. Kang, S. Sakaguchi, D. S. Vinay, and B. S. Kwon
4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells
J. Leukoc. Biol., May 1, 2004; 75(5): 785 - 791.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Suvas, A. K. Azkur, B. S. Kim, U. Kumaraguru, and B. T. Rouse
CD4+CD25+ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions
J. Immunol., April 1, 2004; 172(7): 4123 - 4132.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
S. M. Blois, C. D. Alba Soto, M. Tometten, B. F. Klapp, R. A. Margni, and P. C. Arck
Lineage, Maturity, and Phenotype of Uterine Murine Dendritic Cells Throughout Gestation Indicate a Protective Role in Maintaining Pregnancy
Biol Reprod, April 1, 2004; 70(4): 1018 - 1023.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. Jaffar, T. Sivakuru, and K. Roberts
CD4+CD25+ T Cells Regulate Airway Eosinophilic Inflammation by Modulating the Th2 Cell Phenotype
J. Immunol., March 15, 2004; 172(6): 3842 - 3849.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Hesse, C. A. Piccirillo, Y. Belkaid, J. Prufer, M. Mentink-Kane, M. Leusink, A. W. Cheever, E. M. Shevach, and T. A. Wynn
The Pathogenesis of Schistosomiasis Is Controlled by Cooperating IL-10-Producing Innate Effector and Regulatory T Cells
J. Immunol., March 1, 2004; 172(5): 3157 - 3166.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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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