• 1
    Burchill, M. A., Yang, J., Vang, K. B., Moon, J. J., Chu, H. H., Lio, C. W., Vegoe, A. L. et al., Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity 2008. 28: 112121.
  • 2
    Lio, C. W. and Hsieh, C. S., A two-step process for thymic regulatory T cell development. Immunity 2008. 28: 100111.
  • 3
    Hori, S., Nomura, T. and Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3. Science 2003. 299: 10571061.
  • 4
    Khattri, R., Cox, T., Yasayko, S. A. and Ramsdell, F., An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 2003. 4: 337342.
  • 5
    Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y., Foxp3 programs the development and function of CD4+CD25 +regulatory T cells. Nat. Immunol. 2003. 4: 330336.
  • 6
    Bautista, J. L., Lio, C. W., Lathrop, S. K., Forbush, K., Liang, Y., Luo, J., Rudensky, A. Y. et al., Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat. Immunol. 2009. 10: 610617.
  • 7
    Leung, M. W., Shen, S. and Lafaille, J. J., TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes. J. Exp. Med. 2009. 206: 21212130.
  • 8
    Jordan, M. S., Boesteanu, A., Reed, A. J., Petrone, A. L., Holenbeck, A. E., Lerman, M. A., Naji, A. et al., Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2001. 2: 301306.
  • 9
    Apostolou, I., Sarukhan, A., Klein, L. and von Boehmer, H., Origin of regulatory T cells with known specificity for antigen. Nat. Immunol. 2002. 3: 756763.
  • 10
    Hsieh, C. S., Liang, Y., Tyznik, A. J., Self, S. G., Liggitt, D. and Rudensky, A. Y., Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 2004. 21: 267277.
  • 11
    Hsieh, C. S., Zheng, Y., Liang, Y., Fontenot, J. D. and Rudensky, A. Y., An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 2006. 7: 401410.
  • 12
    Samy, E. T., Parker, L. A., Sharp, C. P. and Tung, K. S., Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node. J. Exp. Med. 2005. 202: 771781.
  • 13
    Setiady, Y. Y., Ohno, K., Samy, E. T., Bagavant, H., Qiao, H., Sharp, C., She, J. X. et al., Physiologic self antigens rapidly capacitate autoimmune disease-specific polyclonal CD4+CD25+ regulatory T cells. Blood 2006. 107: 10561062.
  • 14
    Lathrop, S. K., Santacruz, N. A., Pham, D., Luo, J. and Hsieh, C. S., Antigen-specific peripheral shaping of the natural regulatory T cell population. J. Exp. Med. 2008. 205: 31053117.
  • 15
    Darrasse-Jeze, G., Deroubaix, S., Mouquet, H., Victora, G. D., Eisenreich, T., Yao, K. H., Masilamani, R. F. et al., Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 2009. 206: 18531862.
  • 16
    Poitrasson-Riviere, M., Bienvenu, B., Le Campion, A., Becourt, C., Martin, B. and Lucas, B., Regulatory CD4+ T cells are crucial for preventing CD8+ T cell-mediated autoimmunity. J. Immunol. 2008. 180: 72947304.
  • 17
    Martin, B., Becourt, C., Bienvenu, B. and Lucas, B., Self-recognition is crucial for maintaining the peripheral CD4+ T-cell pool in a nonlymphopenic environment. Blood 2006. 108: 270277.
  • 18
    Grinberg-Bleyer, Y., Baeyens, A., You, S., Elhage, R., Fourcade, G., Gregoire, S., Cagnard, N. et al., IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J. Exp. Med. 2010. 207: 18711878.
  • 19
    Bochtler, P., Wahl, C., Schirmbeck, R. and Reimann, J., Functional adaptive CD4 Foxp3 T cells develop in MHC class II-deficient mice. J. Immunol. 2006. 177: 83078314.
  • 20
    Annacker, O., Pimenta-Araujo, R., Burlen-Defranoux, O., Barbosa, T. C., Cumano, A. and Bandeira, A., CD25 +CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10. J. Immunol. 2001. 166: 30083018.
  • 21
    Takahashi, T., Kuniyasu, Y., Toda, M., Sakaguchi, N., Itoh, M., Iwata, M., Shimizu, J. 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. 1998. 10: 19691980.
  • 22
    Thornton, A. M. and Shevach, E. M., CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998. 188: 287296.
  • 23
    Garbi, N., Hammerling, G. J., Probst, H. C. and van den Broek, M., Tonic T cell signalling and T cell tolerance as opposite effects of self-recognition on dendritic cells. Curr. Opin. Immunol. 2010. 22: 601608.
  • 24
    Gavin, M. A., Clarke, S. R., Negrou, E., Gallegos, A. and Rudensky, A., Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat. Immunol. 2002. 3: 3341.
  • 25
    Tang, Q. and Bluestone, J. A., The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat. Immunol. 2008. 9: 239244.
  • 26
    Wan, Y. Y. and Flavell, R. A., Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007. 445: 766770.
  • 27
    Zhou, X., Bailey-Bucktrout, S. L., Jeker, L. T., Penaranda, C., Martinez-Llordella, M., Ashby, M., Nakayama, M. et al., Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 2009. 10: 10001007.
  • 28
    Hill, J. A., Feuerer, M., Tash, K., Haxhinasto, S., Perez, J., Melamed, R., Mathis, D. et al., Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 2007. 27: 786800.
  • 29
    Komatsu, N., Mariotti-Ferrandiz, M. E., Wang, Y., Malissen, B., Waldmann, H. and Hori, S., Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. U S A 2009. 106: 19031908.
  • 30
    Yu, A., Zhu, L., Altman, N. H. and Malek, T. R., A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells. Immunity 2009. 30: 204217.
  • 31
    Duarte, J. H., Zelenay, S., Bergman, M. L., Martins, A. C. and Demengeot, J., Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 2009. 39: 948955.
  • 32
    Kim, J. K., Klinger, M., Benjamin, J., Xiao, Y., Erle, D. J., Littman, D. R. and Killeen, N., Impact of the TCR signal on regulatory T cell homeostasis, function, and trafficking. PLoS One 2009. 4: e6580.
  • 33
    Tanaka, S., Maeda, S., Hashimoto, M., Fujimori, C., Ito, Y., Teradaira, S., Hirota, K. et al., Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J. Immunol. 2010. 185: 22952305.
  • 34
    Wang, Y., Kissenpfennig, A., Mingueneau, M., Richelme, S., Perrin, P., Chevrier, S., Genton, C. et al., Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells. J. Immunol. 2008. 180: 15651575.
  • 35
    Patton, D. T., Garden, O. A., Pearce, W. P., Clough, L. E., Monk, C. R., Leung, E., Rowan, W. C. et al., Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells. J. Immunol. 2006. 177: 65986602.
  • 36
    Fu, G., Chen, Y., Yu, M., Podd, A., Schuman, J., He, Y., Di, L. et al., Phospholipase C{gamma}1 is essential for T cell development, activation, and tolerance. J. Exp. Med. 2010. 207: 309318.
  • 37
    Madsen, L., Labrecque, N., Engberg, J., Dierich, A., Svejgaard, A., Benoist, C., Mathis, D. et al., Mice lacking all conventional MHC class II genes. Proc. Natl. Acad. Sci. U S A 1999. 96: 1033810343.
  • 38
    Martin, B., Bourgeois, C., Dautigny, N. and Lucas, B., On the role of MHC class II molecules in the survival and lymphopenia-induced proliferation of peripheral CD4+ T cells. Proc. Natl. Acad. Sci. USA 2003. 100: 60216026.
  • 39
    Malissen, M., Gillet, A., Ardouin, L., Bouvier, G., Trucy, J., Ferrier, P., Vivier, E. et al., Altered T cell development in mice with a targeted mutation of the CD3-e gene. EMBO J. 1995. 14: 46414650.
  • 40
    Le Campion, A., Gagnerault, M. C., Auffray, C., Becourt, C., Poitrasson-Riviere, M., Lallemand, E., Bienvenu, B. et al., Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development. Blood 2009. 114: 17841793.