• 1
    Bacchetta, R., Passerini, L., Gambineri, E., Dai, M., Allan, S. E., Perroni, L., Dagna-Bricarelli, F. et al., Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest. 2006. 116: 17131722.
  • 2
    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.
  • 3
    Lan, R. Y., Ansari, A. A., Lian, Z. X. and Gershwin, M. E., Regulatory T cells: development, function and role in autoimmunity. Autoimmun. Rev. 2005. 4: 351363.
  • 4
    Bluestone, J. A. and Tang, Q., Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells. Proc. Natl. Acad. Sci. USA 2004. 101: 1462214626.
  • 5
    Lundsgaard, D., Holm, T. L., Hornum, L. and Markholst, H., In vivo control of diabetogenic T-cells by regulatory CD4+CD25+ T-cells expressing Foxp3. Diabetes 2005. 54: 10401047.
  • 6
    Tarbell, K. V., Yamazaki, S., Olson, K., Toy, P. and Steinman, R. M., CD25+CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 2004. 199: 14671477.
  • 7
    Tarbell, K. V., Petit, L., Zuo, X., Toy, P., Luo, X., Mqadmi, A., Yang, H. et al., Dendritic cell-expanded, islet-specific CD4+CD25+CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med. 2007. 204: 191201.
  • 8
    Tang, Q., Henriksen, K. J., Bi, M., Finger, E. B., Szot, G., Ye, J., Masteller, E. L. et al., In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med. 2004. 199: 14551465.
  • 9
    Brusko, T. M., Wasserfall, C. H., Clare-Salzler, M. J., Schatz, D. A. and Atkinson, M. A., Functional defects and the influence of age on the frequency of CD4+CD25+ T-cells in type 1 diabetes. Diabetes 2005. 54: 14071414.
  • 10
    Lindley, S., Dayan, C. M., Bishop, A., Roep, B. O., Peakman, M. and Tree, T. I., Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 2005. 54: 9299.
  • 11
    Tritt, M., Sgouroudis, E., d'Hennezel, E., Albanese, A. and Piccirillo, C. A., Functional waning of naturally-occurring CD4+ regulatory T cells contributes to the onset of autoimmune diabetes. Diabetes 2008. 57: 113123.
  • 12
    Brusko, T., Wasserfall, C., McGrail, K., Schatz, R., Viener, H. L., Schatz, D., Haller, M. et al., No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Diabetes 2007. 56: 604612.
  • 13
    Sakaguchi, S., The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 2003. 112: 13101312.
  • 14
    Taams, L. S. and Akbar, A. N., Peripheral generation and function of CD4+CD25+ regulatory T cells. Curr. Top. Microbiol. Immunol. 2005. 293: 115131.
  • 15
    Bluestone, J. A. and Abbas, A. K., Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 2003. 3: 253257.
  • 16
    Selvaraj, R. K. and Geiger, T. L., Mitigation of experimental allergic encephalomyelitis by TGF-beta induced Foxp3+ regulatory T lymphocytes through the induction of anergy and infectious tolerance. J. Immunol. 2008. 180: 28302838.
  • 17
    Huter, E. N., Punkosdy, G. A., Glass, D. D., Cheng, L. I., Ward, J. M. and Shevach, E. M., TGF-beta-induced Foxp3(+) regulatory T cells rescue scurfy mice. Eur. J. Immunol. 2008. 38: 18141821.
  • 18
    Godebu, E., Summers-Torres, D., Lin, M. M., Baaten, B. J. and Bradley, L. M., Polyclonal adaptive regulatory CD4 cells that can reverse type I diabetes become oligoclonal long-term protective memory cells. J. Immunol. 2008. 181: 17981805.
  • 19
    Randolph, D. A. and Fathman, C. G., Cd4+Cd25+ regulatory T cells and their therapeutic potential. Annu. Rev. Med. 2006. 57: 381402.
  • 20
    Knoechel, B., Lohr, J., Kahn, E., Bluestone, J. A. and Abbas, A. K., Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J. Exp. Med. 2005. 202: 13751386.
  • 21
    Kang, H. K., Michaels, M. A., Berner, B. R. and Datta, S. K., Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J. Immunol. 2005. 174: 32473255.
  • 22
    Vukmanovic-Stejic, M., Zhang, Y., Cook, J. E., Fletcher, J. M., McQuaid, A., Masters, J. E., Rustin, M. H. et al., Human CD4+CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J. Clin. Invest. 2006. 116: 24232433.
  • 23
    Danke, N. A., Koelle, D. M., Yee, C., Beheray, S. and Kwok, W. W., Autoreactive T cells in healthy individuals. J. Immunol. 2004. 172: 59675972.
  • 24
    Yang, J., James, E. A., Huston, L., Danke, N. A., Liu, A. W. and Kwok, W. W., Multiplex mapping of CD4lT cell epitopes using class II tetramers. Clin. Immunol. 2006. 120: 2132.
  • 25
    Gebe, J. A., Falk, B. A, Rock, K. A., Kochik, S. A., Heninger, A. K., Reijonen, H., Kwok, W. W. and Nepom, G. T., Low-avidity recognition by CD4+ T cells directed to self-antigens. Eur. J. Immunol. 2003. 33: 14091417.
  • 26
    Mallone, R., Kochik, S. A., Laughlin, E. M., Gersuk, V. H., Reijonen, H., Kwok, W. W. and Nepom, G. T., Differential recognition and activation thresholds in human autoreactive GAD-specific T-cells. Diabetes 2004. 53: 971977.
  • 27
    Nepom, G. T. and Erlich, H., MHC class-II molecules and autoimmunity. Annu. Rev. Immunol. 1991. 9: 493525.
  • 28
    Nepom, G. T., Lippolis, J. D., White, F. M., Masewicz, S., Marto, J. A., Herman, A., Luckey, C. J. et al., Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65). Proc. Natl. Acad. Sci. USA 2001. 98: 17631768.
  • 29
    Reijonen, H., Novak, E. J., Kochik, S., Heninger, A., Liu, A. W., Kwok, W. W. and Nepom, G. T., Detection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjects. Diabetes 2002. 51: 13751382.
  • 30
    Danke, N. A., Yang, J., Greenbaum, C. and Kwok, W. W., Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. J. Autoimmun. 2005. 25: 303311.
  • 31
    Yang, J., Danke, N. A., Berger, D., Reichstetter, S., Reijonen, H., Greenbaum, C., Pihoker, C. et al., Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. J. Immunol. 2006. 176: 27812789.
  • 32
    Novak, E. J., Liu, A. W., Nepom, G. T. and Kwok, W. W., MHC class II tetramers identify peptide-specific human CD4(+) T cells proliferating in response to influenza A antigen. J. Clin. Invest. 1999. 104: R63R67.
  • 33
    Allan, S. E., Alstad, A. N., Merindol, N., Crellin, N. K., Amendola, M., Bacchetta, R., Naldini, L. et al., Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol. Ther. 2008. 16: 194202.
  • 34
    Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G. and Levings, M. K., Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 2007. 19: 345354.
  • 35
    Wang, J., Ioan-Facsinay, A., van der Voort, E. I., Huizinga, T. W. and Toes, R. E., Transient expression of FOXP3 in human activated nonregulatory CD4(+) T cells. Eur. J. Immunol. 2007. 37: 129138.
  • 36
    Walker, M. R., Carson, B. D., Nepom, G. T., Ziegler, S. F. and Buckner, J. H., De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25 T cells. Proc. Natl. Acad. Sci. USA 2005. 102: 41034108.
  • 37
    Long, S. A. and Buckner, J. H., Combination of rapamycin and IL-2 increases de novo induction of human CD4(+)CD25(+)FOXP3(+) T cells. J. Autoimmun. 2008. 30: 293302.
  • 38
    Sakaguchi, S. and Sakaguchi, N., Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease. J. Exp. Med. 1990. 172: 537545.
  • 39
    Pacholczyk, R., Kern, J., Singh, N., Iwashima, M., Kraj, P. and Ignatowicz, L., Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity 2007. 27: 493504.
  • 40
    Lin, W., Haribhai, D., Relland, L., Truong, N., Carlson, M., Williams, C. and Chatila, T., Regulatory T cell development in the absence of functional Foxp3. Nat. Immunol. 2007. 8: 359368.
  • 41
    Gavin, M. A., Torgerson, T. R., Houston, E., DeRoos, P., Ho, W. Y., Stray-Pedersen, A., Ocheltree, E. L. et al., Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl. Acad. Sci. USA 2006. 103: 66596664.
  • 42
    Liu, W., Putnam, A. L., Xu-Yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A. et al., CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 2006. 203: 17011711.
  • 43
    Weber, S. E., Harbertson, J., Godebu, E., Mros, G. A., Padrick, R. C., Carson, B. D., Ziegler, S. F. and Bradley, L. M., Adaptive islet-specific regulatory CD4lT cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J. Immunol. 2006. 176: 47304739.