• 1
    Thornton, A. M., Donovan, E. E., Piccirillo, C. A. and Shevach, E. M., Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J. Immunol. 2004. 172: 65196523.
  • 2
    Thornton, A. M., Piccirillo, C. A. and Shevach, E. M., Activation requirements for the induction of CD4+CD25+ T cell suppressor function. Eur. J. Immunol. 2004. 34: 366376.
  • 3
    Takahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., Mak, T. W. et al., Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000. 192: 303310.
  • 4
    Paul, W. E., Fundamental immunology , Lippincott Williams & Wilkins, Philadelphia 2003, 5th Edn.
  • 5
    Sansom, D. M. and Walker, L. S., The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology. Immunol. Rev. 2006. 212: 131148.
  • 6
    Ziegler, S. F., FOXP3: of mice and men. Annu. Rev. Immunol. 2006. 24: 209226.
  • 7
    Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A., Paeper, B., Clark, L. B., Yasayko, S. A., Wilkinson, J. E. et al., Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 2001. 27: 6873.
  • 8
    Chatila, T. A., Blaeser, F., Ho, N., Lederman, H. M., Voulgaropoulos, C., Helms, C. and Bowcock, A. M., JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J. Clin. Invest. 2000. 106: R7581.
  • 9
    Hori, S., Nomura, T. and Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3. Science 2003. 299: 10571061.
  • 10
    Cohen, A. C., Nadeau, K. C., Tu, W., Hwa, V., Dionis, K., Bezrodnik, L., Teper, A. et al., Cutting edge: Decreased accumulation and regulatory function of CD4+ CD25(high) T cells in human STAT5b deficiency. J. Immunol. 2006. 177: 27702774.
  • 11
    Doganci, A., Eigenbrod, T., Krug, N., De Sanctis, G. T., Hausding, M., Erpenbeck, V. J., Haddad el, B. et al., The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J. Clin. Invest. 2005. 115: 313325.
  • 12
    Kolls, J. K. and Linden, A., Interleukin-17 family members and inflammation. Immunity 2004. 21: 467476.
  • 13
    Pasare, C. and Medzhitov, R., Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 2003. 299: 10331036.
  • 14
    Fehervari, Z. and Sakaguchi, S., Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells. Int. Immunol. 2004. 16: 17691780.
  • 15
    Kubo, T., Hatton, R. D., Oliver, J., Liu, X., Elson, C. O. and Weaver, C. T., Regulatory T cell suppression and anergy are differentially regulated by proinflammatory cytokines produced by TLR-activated dendritic cells. J. Immunol. 2004. 173: 72497258.
  • 16
    Alexander, W. S. and Hilton, D. J., The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu. Rev. Immunol. 2004. 22: 503529.
  • 17
    Bode, J. G., Ludwig, S., Ehrhardt, C., Albrecht, U., Erhardt, A., Schaper, F., Heinrich, P. C. et al., IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. FASEB J. 2003. 17: 488490.
  • 18
    Cohney, S. J., Sanden, D., Cacalano, N. A., Yoshimura, A., Mui, A., Migone, T. S. and Johnston, J. A., SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. Mol. Cell. Biol. 1999. 19: 49804988.
  • 19
    Croker, B. A., Krebs, D. L., Zhang, J. G., Wormald, S., Willson, T. A., Stanley, E. G., Robb, L. et al., SOCS3 negatively regulates IL-6 signaling invivo. Nat. Immunol. 2003. 4: 540545.
  • 20
    Jo, D., Liu, D., Yao, S., Collins, R. D. and Hawiger, J., Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat. Med. 2005. 11: 892898.
  • 21
    Seki, Y., Inoue, H., Nagata, N., Hayashi, K., Fukuyama, S., Matsumoto, K., Komine, O. et al., SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat. Med. 2003. 9: 10471054.
  • 22
    Shouda, T., Yoshida, T., Hanada, T., Wakioka, T., Oishi, M., Miyoshi, K., Komiya, S. et al., Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J. Clin. Invest. 2001. 108: 17811788.
  • 23
    Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T. et al., IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat. Immunol. 2003. 4: 551556.
  • 24
    Lang, R., Pauleau, A. L., Parganas, E., Takahashi, Y., Mages, J., Ihle, J. N., Rutschman, R. et al., SOCS3 regulates the plasticity of gp130 signaling. Nat. Immunol. 2003. 4: 546550.
  • 25
    Yu, C. R., Mahdi, R. M., Ebong, S., Vistica, B. P., Gery, I. and Egwuagu, C. E., Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells. J. Biol. Chem. 2003. 278: 2975229759.
  • 26
    Banerjee, D. K., Dhodapkar, M. V., Matayeva, E., Steinman, R. M. and Dhodapkar, K. M., Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients. Blood 2006. 108: 26552661.
  • 27
    Liu, H., Hu, B., Xu, D. and Liew, F. Y., CD4+CD25+ regulatory T cells cure murine colitis: the role of IL-10, TGF-beta, and CTLA4. J. Immunol. 2003. 171: 50125017.
  • 28
    Kataoka, H., Takahashi, S., Takase, K., Yamasaki, S., Yokosuka, T., Koike, T. and Saito, T., CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4. Int. Immunol. 2005. 17: 421427.
  • 29
    Wan, Y. Y. and Flavell, R. A., Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007. 445: 766770.
  • 30
    Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A. and Rudensky, A. Y., Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007. 445: 771775.
  • 31
    Haan, S., Ferguson, P., Sommer, U., Hiremath, M., McVicar, D. W., Heinrich, P. C., Johnston, J. A. et al., Tyrosine phosphorylation disrupts elongin interaction and accelerates SOCS3 degradation. J. Biol. Chem. 2003. 278: 3197231979.
  • 32
    Fontenot, J. D., Rasmussen, J. P., Gavin, M. A. and Rudensky, A. Y., A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat. Immunol. 2005. 6: 11421151.
  • 33
    Zheng, Y., Josefowicz, S. Z., Kas, A., Chu, T. T., Gavin, M. A. and Rudensky, A. Y., Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 2007. 445: 936940.
  • 34
    Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G. and Rudensky, A. Y., Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005. 22: 329341.
  • 35
    Sugimoto, N., Oida, T., Hirota, K., Nakamura, K., Nomura, T., Uchiyama, T. and Sakaguchi, S., Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 2006. 18: 11971209.
  • 36
    Cornish, A. L., Chong, M. M., Davey, G. M., Darwiche, R., Nicola, N. A., Hilton, D. J., Kay, T. W. et al., Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other gamma c-dependent cytokines in peripheral T cells. J. Biol. Chem. 2003. 278: 2275522761.
  • 37
    Nicholson, S. E., Willson, T. A., Farley, A., Starr, R., Zhang, J. G., Baca, M., Alexander, W. S. et al., Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 1999. 18: 375385.
  • 38
    Metcalf, D., Greenhalgh, C. J., Viney, E., Willson, T. A., Starr, R., Nicola, N. A., Hilton, D. J. et al., Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 2000. 405: 10691073.
  • 39
    Xu, H., Williams, M. S. and Spain, L. M., Patterns of expression, membrane localization, and effects of ectopic expression suggest a function for MS4a4B, a CD20 homolog in Th1 T cells. Blood 2006. 107: 24002408.
  • 40
    Kinjyo, I., Inoue, H., Hamano, S., Fukuyama, S., Yoshimura, T., Koga, K., Takaki, H. et al., Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J. Exp. Med. 2006. 203: 10211031.
  • 41
    Ostroukhova, M., Seguin-Devaux, C., Oriss, T. B., Dixon-McCarthy, B., Yang, L., Ameredes, B. T., Corcoran, T. E. et al., Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-beta and FOXP3. J. Clin. Invest. 2004. 114: 2838.
  • 42
    Ostroukhova, M., Qi, Z., Oriss, T. B., Dixon-McCarthy, B., Ray, P. and Ray, A., Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF-beta. J. Clin. Invest. 2006. 116: 9961004.
  • 43
    Ogata, H., Kobayashi, T., Chinen, T., Takaki, H., Sanada, T., Minoda, Y., Koga, K. et al., Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology 2006. 131: 179193.
  • 44
    Yurchenko, E., Tritt, M., Hay, V., Shevach, E. M., Belkaid, Y. and Piccirillo, C. A., CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence. J. Exp. Med. 2006. 203: 24512460.
  • 45
    Ishida, T., Ishii, T., Inagaki, A., Yano, H., Komatsu, H., Iida, S., Inagaki, H. et al., Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res. 2006. 66: 57165722.
  • 46
    Zhang, D. H., Cohn, L., Ray, P., Bottomly, K. and Ray, A., Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J. Biol. Chem. 1997. 272: 2159721603.
  • 47
    Pear, W. S., Miller, J. P., Xu, L., Pui, J. C., Soffer, B., Quackenbush, R. C., Pendergast, A. M. et al., Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood 1998. 92: 37803792.