CD4+CD25+ suppressor T cells: more questions than answers (original) (raw)
Gershon, R. K. & Kondo, K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology18, 723–735 (1970). CASPubMedPubMed Central Google Scholar
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains. J. Immunol.155, 1151–1164 (1995).The first paper to show that CD25 can be used as a marker for suppressor T cells. CASPubMed Google Scholar
Asano, M., Toda, M., Sakaguchi, N. & Sakaguchi, S. Autoimmune disease as a consequence of developmental abnormality of a T-cell subpopulation. J. Exp. Med.184, 387–396 (1996). ArticleCASPubMed Google Scholar
Thornton, A. M. & Shevach, E. M. CD4+CD25+ immunoregulatory T cells suppress polyclonal T-cell activation in vitro by inhibiting interleukin-2 production. J. Exp. Med.188, 287–296 (1998).A comprehensive analysis of thein vitrofunction of CD4+CD25+ T cells. ArticleCASPubMedPubMed Central Google Scholar
Takahashi, T. et al. 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, 1969–1980 (1998). ArticleCASPubMed Google Scholar
Read, S. et al. CD38+CD45RBlow T cells: a population of T cells with immune regulatory activities in vitro. Eur. J. Immunol.28, 3435–3447 (1998). ArticleCASPubMed Google Scholar
Levings, M. K., Sangregorio, R. & Roncarolo, M.-G. Human CD25+CD4+ T cells suppress naive and memory T-cell proliferation and can be expanded in vitro without loss of suppressor function. J. Exp. Med.193, 1295–1302 (2001). ArticleCASPubMedPubMed Central Google Scholar
Dieckmann, D., Plottner, H., Berchtold, S., Berger, T. & Schuler, G. Ex vivo isolation and characterization of CD4+CD25+ T cells with regulatory properties from human blood. J. Exp. Med.193, 1303–1310 (2001). ArticleCASPubMedPubMed Central Google Scholar
Jonuleit, H. et al. Identification and functional characterization of human CD4+CD25+ T cells with regulatory properties isolated from peripheral blood. J. Exp. Med.193, 1285–1294 (2001). ArticleCASPubMedPubMed Central Google Scholar
Taams, L. S. et al. Human anergic suppressive CD4+CD25+ T cells: a highly differentiated and apoptosis-prone population. Eur. J. Immunol.31, 1122–1131 (2001). ArticleCASPubMed Google Scholar
Stephens, L. A., Mottet, C., Mason, D. & Powrie, F. Human CD4+CD25+ thymocytes and peripheral T cells have immune suppressive activity. Eur. J. Immunol.31, 1247–1254 (2001). ArticleCASPubMed Google Scholar
Ng, W. F. et al. Human CD4+CD25+ cells: a naturally occurring population of regulatory T cells. Blood98, 2736–2744 (2001). ArticleCASPubMed Google Scholar
Baecher-Allen, C., Brown, J. A., Freeman, G. J. & Hafler, D. A. CD4+CD25+ regulatory cells in human peripheral blood. J. Immunol.167, 1245–1253 (2001). Article Google Scholar
Chen, Y., Kuchroo, V. K., Inobe, J.-I., Hafler, D. A. & Weiner, H. L. Regulatory T-cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science265, 1237–1240 (1994). ArticleCASPubMed Google Scholar
Sakaguchi, S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell101, 455–458 (2000). ArticleCASPubMed Google Scholar
Maloy, K. J. & Powrie, F. Regulatory T cells in the control of immune pathology. Nature Immunol.2, 816–822 (2001). ArticleCAS Google Scholar
Thornton, A. M. & Shevach, E. M. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol.164, 183–190 (2000). ArticleCASPubMed Google Scholar
Takahashi, T. et al. Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic lymphocyte-associated antigen 4. J. Exp. Med.192, 303–309 (2000). ArticleCASPubMedPubMed Central Google Scholar
Read, S., Malmstrom, V. & Powrie, F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J. Exp. Med.192, 295–302 (2000). CASPubMedPubMed Central Google Scholar
Nakamura, K., Kitani, A. & Strober, W. Cell contact-dependent immunosuppression by CD4+CD25+ regulatory T cells is mediated by cell-surface-bound transforming growth factor-β. J. Exp. Med.194, 629–644 (2001). ArticleCASPubMedPubMed Central Google Scholar
Letterio, J. J. & Roberts, A. B. Regulation of immune responses by TGF-β. Annu. Rev. Immunol.16, 137–161 (1998). ArticleCASPubMed Google Scholar
Yang, X. et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T-cell responsiveness to TGF-β. EMBO J.18, 1280–1291 (1999). ArticleCASPubMedPubMed Central Google Scholar
Lucas, P. J., Kim, S. J., Melby, S. J. & Gress, R. E. Disruption of T-cell homeostasis in mice expressing a T-cell-specific dominant-negative transforming growth factor-βII receptor. J. Exp. Med.191, 1187–1196 (2000). ArticleCASPubMedPubMed Central Google Scholar
Kulkarni, A. B. et al. Transforming growth factor-β1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl Acad. Sci. USA90, 770–774 (1993). ArticleCASPubMedPubMed Central Google Scholar
Cederbom, L., Hall, H. & Ivars, F. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur. J. Immunol.30, 1538–1543 (2000). ArticleCASPubMed Google Scholar
Piccirillo, C. & Shevach, E. M. Cutting edge: control of CD8+ T-cell activation by CD4+CD25+ immunoregulatory cells. J. Immunol.167, 1137–1140 (2001). ArticleCASPubMed Google Scholar
Desbarats, J., Duke, R. C. & Newell, M. K. Newly discovered role for Fas ligand in the cell-cycle arrest of CD4+ T cells. Nature Med.4, 1377–1382 (1998). ArticleCASPubMed Google Scholar
McHugh, R. S. et al. CD4+CD25+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity16, 311–323 (2002). ArticleCASPubMed Google Scholar
Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y. & Sakaguchi, S. Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nature Immunol.3, 135–142 (2002). ArticleCAS Google Scholar
Sinclair, N. R. S. Immunoreceptor tyrosine-based inhibitory motifs on activating molecules. Crit. Rev. Immunol.20, 89–102 (2000). ArticleCASPubMed Google Scholar
Burshtyn, D. N. & Long, E. O. Regulation through inhibitory receptors: lessons from natural killer cells. Trends Cell Biol.7, 473–479 (1997). ArticleCASPubMed Google Scholar
Asseman, C., Mauze, S., Leach, M. W., Coffman, R. L. & Powrie, F. An essential role for interleukin-10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med.190, 995–1003 (1999). ArticleCASPubMedPubMed Central Google Scholar
McHugh, R. S., Shevach, E. M. & Thornton, A. M. Control of organ-specific autoimmunity by immunoregulatory CD4+CD25+ T cells. Microbes Infect.3, 919–927 (2001). ArticleCASPubMed Google Scholar
Seddon, B. & Mason, D. Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor-β and interleukin-4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4+CD45RC− cells and CD4+CD8− thymocytes. J. Exp. Med.189, 279–288 (1999). ArticleCASPubMedPubMed Central Google Scholar
Suri-Payer, E. & Cantor, H. Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4+CD25+ T cells. J. Autoimmun.16, 115–123 (2001). ArticleCASPubMed Google Scholar
Grande, J. P. Role of transforming growth factor-β in tissue injury and repair. Proc. Soc. Exp. Biol. Med.214, 27–40 (1997). ArticleCASPubMed Google Scholar
Stockinger, B., Barthlott, T. & Kassiotis, G. T-cell regulation: a special job or everyone's responsibility? Nature Immunol.2, 757–758 (2001). ArticleCAS Google Scholar
Suri-Payer, E., Amar, A. Z., Thornton, A. M. & Shevach, E. M. CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J. Immunol.160, 1212–1218 (1998). CASPubMed Google Scholar
Bonomo, A., Kehn, P. J. & Shevach, E. M. Post-thymectomy autoimmunity-abnormal T-cell homeostasis. Immunol. Today16, 61–67 (1995). ArticleCASPubMed Google Scholar
Papiernik, M., de Moraes, M. L., Pontoux, C., Vasseur, F. & Penit, C. Regulatory CD4 T cells: expression of IL-2R α-chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol.10, 371–378 (1998). ArticleCASPubMed Google Scholar
Itoh, M. et al. 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, 5317–5326 (1999). CASPubMed Google Scholar
Jordan, M. S. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nature Immunol.2, 301–306 (2001). ArticleCAS Google Scholar
Bensinger, S. J., Bandeira, A., Jordan, M. S., Caton, A. J. & Laufer, T. M. Major histocompatibility complex class-II-positive cortical epithelium mediates the selection of CD4+CD25+ immunoregulatory T cells. J. Exp. Med.194, 427–438 (2001).A clear genetic demonstration that CD4+CD25+ T cells can be selected on thymic cortical epithelium. ArticleCASPubMedPubMed Central Google Scholar
Laufer, T. M. et al. Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature383, 81–85 (1996). ArticleCASPubMed Google Scholar
Malek, T. R., Porter, B. O., Codias, E. K., Scibelli, P. & Yu, A. Normal lymphoid homeostasis and lack of lethal autoimmunity in mice containing mature T cells with severely impaired IL-2 receptors. J. Immunol.164, 2905–2914 (2000). CASPubMed Google Scholar
Kagami, S.-I. et al. Stat5a regulates T helper cell differentiation by several distinct mechanisms. Blood97, 2358–2365 (2001). ArticleCASPubMed Google Scholar
Suzuki, H., Zhou, Y. W., Kato, M., Mak, T. W. & Nakashima, I. Normal regulatory αβ T cells effectively eliminate abnormally activated T cells lacking the interleukin-2 receptor-β in vivo. J. Exp. Med.190, 1561–1571 (1999). ArticleCASPubMedPubMed Central Google Scholar
Kumanogoh, A. et al. Increased T-cell autoreactivity in the absence of CD40–CD40 ligand interactions: a role of CD40 regulatory T-cell development. J. Immunol.166, 353–360 (2001). ArticleCASPubMed Google Scholar
Salomon, B. et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity12, 431–440 (2000).The first demonstration that CD4+CD25+ T cells have a role in regulating diabetes in NOD mice. ArticleCASPubMed Google Scholar
Wolf, M., Schimpl, A. & Hunig, T. Control of T-cell hyperactivation in IL-2-deficient mice by CD4+CD25− and CD4+CD25+ T cells: evidence for two distinct regulatory mechanisms. Eur. J. Immunol.31, 1637–1645 (2001). ArticleCASPubMed Google Scholar
Taguchi, O. & Nishizuka, Y. Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self-tolerance. J. Exp. Med.165, 146–156 (1987). ArticleCASPubMed Google Scholar
Taguchi, O. et al. Tissue-specific suppressor T cells involved in self-tolerance are activated extrathymically by self-antigens. Immunology82, 365–369 (1994). CASPubMedPubMed Central Google Scholar
McCullagh, P. The significance of immune suppression in normal self tolerance. Immunol. Rev.149, 127–154 (1996). ArticleCASPubMed Google Scholar
Seddon, B. & Mason, D. Peripheral autoantigen induces regulatory T cells that prevent autoimmunity. J. Exp. Med.189, 877–881 (1999).The most convincing study to show that regulatory T cells recognize organ-specific antigens. ArticleCASPubMedPubMed Central Google Scholar
Garza, K. M., Agersborg, S. S., Baker, E. & Tung, K. S. T. Persistence of physiological antigen is required for the regulation of self-tolerance. J. Immunol.164, 3982–3989 (2000). ArticleCASPubMed Google Scholar
McHugh, R. S., Shevach, E. M., Margulies, D. H. & Natarajan, K. A T-cell receptor transgenic model of severe, spontaneous organ-specific autoimmunity. Eur. J. Immunol.31, 2094–2103 (2001). ArticleCASPubMed Google Scholar
Iellem, A. et al. Unique chemotactic response profile and specific expression of chemokine receptors on CCR4 and CCR8 by CD4+CD8+ regulatory T cells. J. Exp. Med.194, 847–853 (2001). ArticleCASPubMedPubMed Central Google Scholar
Bystry, R. S. et al. B cells and professional APCs recruit regulatory T cells via CCL4. Nature Immunol.2, 1126–1152 (2001). ArticleCAS Google Scholar
Olivares-Villagomez, D., Wang, Y. & Lafaille, J. J. Regulatory CD4+ T cells expressing endogenous T-cell receptor chains protect myelin basic protein-specific transgenic mice from spontanteous autoimmune encephalomyelitis. J. Exp. Med.188, 1883–1894 (1998). ArticleCASPubMedPubMed Central Google Scholar
Olivares–Villagomez, D., Wensky, A. K., Wang, Y. & Lafaille, J. J. Repertoire requirements of CD4+ T cells that prevent spontaneous autoimmune encephalomyelitis. J. Immunol.164, 5499–5507 (2000). ArticlePubMed Google Scholar
Annacker, O., Burlen-Defranoux, O., Pimenta-Araujo, R., Cumano, A. & Bandeira, A. Regulatory CD4 T cells control the size of the peripheral activated/memory CD4 T-cell compartment. J. Immunol.164, 3573–3580 (2000). ArticleCASPubMed Google Scholar
Stephens, L. A. & Mason, D. CD25 is a marker for CD4+ thymocytes that prevent autoimmune diabetes in rats, but peripheral T cells with this function are found in both CD25+ and CD25− subpopulations. J. Immunol.165, 3105–3110 (2000). ArticleCASPubMed Google Scholar
Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific TD-cell responses and prevents colitis. Nature389, 737–742 (1997).The first definition of the TR1 population of regulatory T cells. ArticleCASPubMed Google Scholar
Levings, M. K. et al. IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol.166, 5530–5539 (2001). ArticleCASPubMed Google Scholar
Jonuleit, H., Schmitt, E., Schuler, G., Knop, J. & Enk, A. H. Induction of interleukin-10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature dendritic cells. J. Exp. Med.192, 1213–1222 (2000). CASPubMedPubMed Central Google Scholar
Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, C. & Bhardwaj, N. Antigen-specific inhibition of effector T-cell function in humans after injection of immature dendritic cells. J. Exp. Med.193, 233–238 (2001). CASPubMedPubMed Central Google Scholar
Yamagiwa, S., Gray, J. D., Hashimoto, S. & Horwitz, D. A. A role of TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J. Immunol.166, 7282–7289 (2001). ArticleCASPubMed Google Scholar
Gregori, S. et al. Regulatory T cells induced by 1α,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J. Immunol.167, 1945–1953 (2001). ArticleCASPubMed Google Scholar
Allison, A. C. & Eugui, E. M. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin. Transplant.10, 77–84 (1996). CASPubMed Google Scholar
Mehling, A. et al. Mycophenolate mofetil impairs the maturation and function of murine dendritic cells. J. Immunol.165, 2374–2381 (2000). ArticleCASPubMed Google Scholar
Hara, M. et al. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol.166, 3789–3796 (2001). ArticleCASPubMed Google Scholar
Vendetti, S. et al. Anergic T cells inhibit the antigen-presenting function of dendritic cells. J. Immunol.165, 1175–1181 (2000). ArticleCASPubMed Google Scholar
Taams, L. S., Boot, E. P. J., van Eden, W. & Wauben, M. H. M. 'Anergic' T cells modulate the T-cell activating capacity of antigen-presenting cells. J. Autoimmun.14, 335–341 (2000). ArticleCASPubMed Google Scholar
Thorstenson, K. M. & Khoruts, A. Generation of anergic and potentially immunoregulatory CD25+CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J. Immunol.167, 188–195 (2001). ArticleCASPubMed Google Scholar
Onizuka, S. et al. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor-α) monoclonal antibody. Cancer Res.59, 3128–3133 (1999). CASPubMed Google Scholar
Shimizu, J., Yamazaki, S. & Sakaguchi, S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol.163, 5211–5218 (1999). CASPubMed Google Scholar
Sutmuller, R. P. et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25+ regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T-lymphocyte responses. J. Exp. Med.194, 823–832 (2001).This study indicates an important role for CD4+CD25+ T cells in preventing the induction of tumour immunity that is independent of CTLA4. ArticleCASPubMedPubMed Central Google Scholar
Bloom, B. R., Modlin, R. L. & Salgame, P. Stigma variations: observations on suppressor T cells and leprosy. Annu. Rev. Immunol.10, 453–488 (1992). ArticleCASPubMed Google Scholar
Belkaid, Y. et al. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. J. Exp. Med.194, 1497–1506 (2001). ArticleCASPubMedPubMed Central Google Scholar
McHugh, R. S. & Shevach, E. M. Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not sufficient, for the induction of organ-specific autoimmune disease. J. Immunol. (in the press).