• 1
    Hariharan, S., Johnson, C. P., Bresnahan, B. A., Taranto, S. E., McIntosh, M. J. and Stablein, D., Improved graft survival after renal transplantation in the United States, 1988 to 1996. N. Engl. J. Med. 2000. 342: 605612.
  • 2
    Meier-Kriesche, H. U., Schold, J. D., Srinivas, T. R. and Kaplan, B., Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am. J. Transplant. 2004. 4: 378383.
  • 3
    Buell, J. F., Gross, T. G. and Woodle, E. S., Malignancy after transplantation. Transplantation 2005. 80: S254S264.
  • 4
    Fishman, J. A., Infection in solid-organ transplant recipients. N. Engl. J. Med. 2007. 357: 26012614.
  • 5
    Chatenoud, L. and Bluestone, J. A., CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat. Rev. Immunol. 2007. 7: 622632.
  • 6
    Bloom, D. D., Chang, Z., Fechner, J. H., Dar, W., Polster, S. P., Pascual, J., Turka, L. A. and Knechtle, S. J., CD4+CD25+FOXP3+regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am. J. Transplant. 2008. 8: 793802.
  • 7
    Clatworthy, M. R., Friend, P. J., Calne, R. Y., Rebello, P. R., Hale, G., Waldmann, H. and Watson, C. J., Alemtuzumab (CAMPATH-1H) for the treatment of acute rejection in kidney transplant recipients: long-term follow-up. Transplantation 2009. 87: 10921095.
  • 8
    Fontenot, J. D., Dooley, J. L., Farr, A. G. and Rudensky, A. Y., Developmental regulation of Foxp3 expression during ontogeny. J. Exp. Med. 2005. 202: 901906.
  • 9
    Hori, S., Nomura, T. and Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3. Science 2003. 299: 10571061.
  • 10
    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.
  • 11
    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.
  • 12
    Wildin, R. S., Ramsdell, F., Peake, J., Faravelli, F., Casanova, J. L., Buist, N., Levy-Lahad, E. et al., X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 2001. 27: 1820.
  • 13
    Lahl, K., Loddenkemper, C., Drouin, C., Freyer, J., Arnason, J., Eberl, G., Hamann, A. et al., Selective depletion of Foxp3+regulatory T cells induces a scurfy-like disease. J. Exp. Med. 2007. 204: 5763.
  • 14
    Kim, J. M., Rasmussen, J. P. and Rudensky, A. Y., Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 2007. 8: 191197.
  • 15
    Aluvihare, V. R., Kallikourdis, M. and Betz, A. G., Regulatory T cells mediate maternal tolerance to the fetus. Nat. Immunol. 2004. 5: 266271.
  • 16
    Zou, W., Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol. 2006. 6: 295307.
  • 17
    Suffia, I. J., Reckling, S. K., Piccirillo, C. A., Goldszmid, R. S. and Belkaid, Y., Infected site-restricted Foxp3+natural regulatory T cells are specific for microbial antigens. J. Exp. Med. 2006. 203: 777788.
  • 18
    Wood, K. J. and Sakaguchi, S., Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 2003. 3: 199210.
  • 19
    Qin, S., Cobbold, S. P., Pope, H., Elliott, J., Kioussis, D., Davies, J. and Waldmann, H., “Infectious” transplantation tolerance. Science 1993. 259: 974977.
  • 20
    Bushell, A. and Wood, K., GITR Ligation Blocks Allograft Protection by Induced CD25(+)CD4(+) Regulatory T Cells without Enhancing Effector T-Cell Function. Am. J. Transplant. 2007. 7: 759768.
  • 21
    Kingsley, C. I., Karim, M., Bushell, A. R. and Wood, K. J., CD25+CD4+regulatory T cells prevent graft rejection: CTLA-4- and IL-10-dependent immunoregulation of alloresponses. J. Immunol. 2002. 168: 10801086.
  • 22
    Hara, M., Kingsley, C. I., Niimi, M., Read, S., Turvey, S. E., Bushell, A. R., Morris, P. J. et al., IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol. 2001. 166: 37893796.
  • 23
    Hall, B. M., Pearce, N. W., Gurley, K. E. and Dorsch, S. E., Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+suppressor cell and its mechanisms of action. J. Exp. Med. 1990. 171: 141157.
  • 24
    Karim, M., Kingsley, C. I., Bushell, A. R., Sawitzki, B. S. and Wood, K. J., Alloantigen-induced CD25+CD4+regulatory T cells can develop in vivo from CD25-CD4+precursors in a thymus-independent process. J. Immunol. 2004. 172: 923928.
  • 25
    Saitovitch, D., Bushell, A., Mabbs, D. W., Morris, P. J. and Wood, K. J., Kinetics of induction of transplantation tolerance with a nondepleting anti-Cd4 monoclonal antibody and donor-specific transfusion before transplantation. A critical period of time is required for development of immunological unresponsiveness. Transplantation 1996. 61: 16421647.
  • 26
    Sanchez-Fueyo, A., Tian, J., Picarella, D., Domenig, C., Zheng, X. X., Sabatos, C. A., Manlongat, N. et al., Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat. Immunol. 2003. 4: 10931101.
  • 27
    Graca, L., Thompson, S., Lin, C. Y., Adams, E., Cobbold, S. P. and Waldmann, H., Both CD4(+)CD25(+) and CD4(+)CD25(-) regulatory cells mediate dominant transplantation tolerance. J. Immunol. 2002. 168: 55585565.
  • 28
    Mannon, R. B. and Kirk, A. D., Beyond histology: novel tools to diagnose allograft dysfunction. Clin. J. Am. Soc. Nephrol. 2006. 1: 358366.
  • 29
    Oliveira, V., Sawitzki, B., Chapman, S., Appelt, C., Gebuhr, I., Wieckiewicz, J., Long, E. and Wood, K. J., Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection. Eur. J. Immunol. 2008. 38: 16771688.
  • 30
    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.
  • 31
    Apostolou, I. and von Boehmer, H., In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 2004. 199: 14011408.
  • 32
    Cobbold, S. P., Castejon, R., Adams, E., Zelenika, D., Graca, L., Humm, S. and Waldmann, H., Induction of foxP3+regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J. Immunol. 2004. 172: 60036010.
  • 33
    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.
  • 34
    Moxham, V. F., Karegli, J., Phillips, R. E., Brown, K. L., Tapmeier, T. T., Hangartner, R., Sacks, S. H. and Wong, W., Homeostatic proliferation of lymphocytes results in augmented memory-like function and accelerated allograft rejection. J. Immunol. 2008. 180: 39103918.
  • 35
    Blais, M. E., Brochu, S., Giroux, M., Belanger, M. P., Dulude, G., Sekaly, R. P. and Perreault, C., Why T cells of thymic versus extrathymic origin are functionally different. J. Immunol. 2008. 180: 22992312.
  • 36
    Hricik, D. E., Rodriguez, V., Riley, J., Bryan, K., Tary-Lehmann, M., Greenspan, N., Dejelo, C. et al., Enzyme linked immunosorbent spot (ELISPOT) assay for interferon-gamma independently predicts renal function in kidney transplant recipients. Am. J. Transplant. 2003. 3: 878884.
  • 37
    Nickel, P., Presber, F., Bold, G., Biti, D., Schonemann, C., Tullius, S. G., Volk, H. D. and Reinke, P., Enzyme-linked immunosorbent spot assay for donor-reactive interferon-gamma-producing cells identifies T-cell presensitization and correlates with graft function at 6 and 12 months in renal-transplant recipients. Transplantation 2004. 78: 16401646.
  • 38
    Poggio, E. D., Clemente, M., Riley, J., Roddy, M., Greenspan, N. S., Dejelo, C., Najafian, N. et al., Alloreactivity in renal transplant recipients with and without chronic allograft nephropathy. J. Am. Soc. Nephrol. 2004. 15: 19521960.
  • 39
    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.
  • 40
    Tsuji, M., Komatsu, N., Kawamoto, S., Suzuki, K., Kanagawa, O., Honjo, T., Hori, S. and Fagarasan, S., Preferential generation of follicular B helper T cells from Foxp3+T cells in gut Peyer's patches. Science 2009. 323: 14881492.
  • 41
    Zhou, L., Chong, M. M. and Littman, D. R., Plasticity of CD4+T cell lineage differentiation. Immunity 2009. 30: 646655.
  • 42
    Zhou, L., Lopes, J. E., Chong, M. M., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y. et al., TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008. 453: 236240.
  • 43
    Kielian, T., Toll-like Receptors: Roles in Infection and Neuropathology. Springer-Verlag: Heidelberg 2009.
  • 44
    Chen, L., Wang, T., Zhou, P., Ma, L., Yin, D., Shen, J., Molinero, L. et al., TLR engagement prevents transplantation tolerance. Am. J. Transplant. 2006. 6: 22822291.
  • 45
    Curotto de Lafaille, M. A., Lino, A. C., Kutchukhidze, N. and Lafaille, J. J., CD25- T cells generate CD25+Foxp3+regulatory T cells by peripheral expansion. J. Immunol. 2004. 173: 72597268.
  • 46
    Liang, S., Alard, P., Zhao, Y., Parnell, S., Clark, S. L. and Kosiewicz, M. M., Conversion of CD4+CD25- cells into CD4+CD25+regulatory T cells in vivo requires B7 costimulation, but not the thymus. J. Exp. Med. 2005. 201: 127137.
  • 47
    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.
  • 48
    Nagahama, K., Fehervari, Z., Oida, T., Yamaguchi, T., Ogawa, O. and Sakaguchi, S., Differential control of allo-antigen-specific regulatory T cells and effector T cells by anti-CD4 and other agents in establishing transplantation tolerance. Int. Immunol. 2009. 21: 379391.
  • 49
    Carvalho-Gaspar, M., Jones, N. D., Luo, S., Martin, L., Brook, M. O. and Wood, K. J., Location and time-dependent control of rejection by regulatory T cells culminates in a failure to generate memory T cells. J. Immunol. 2008. 180: 66406648.
  • 50
    Yang, J., Brook, M. O., Carvalho-Gaspar, M., Zhang, J., Ramon, H. E., Sayegh, M. H., Wood, K. J. et al., Allograft rejection mediated by memory T cells is resistant to regulation. Proc. Natl. Acad. Sci. USA 2007. 104: 1995419959.
  • 51
    Iwakoshi, N. N., Mordes, J. P., Markees, T. G., Phillips, N. E., Rossini, A. A. and Greiner, D. L., Treatment of allograft recipients with donor-specific transfusion and anti-CD154 antibody leads to deletion of alloreactive CD8+T cells and prolonged graft survival in a CTLA4-dependent manner. J. Immunol. 2000. 164: 512521.
  • 52
    Wells, A. D., Li, X. C., Li, Y., Walsh, M. C., Zheng, X. X., Wu, Z., Nunez, G. et al., Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Nat. Med. 1999. 5: 13031307.
  • 53
    Lechler, R. I., Garden, O. A. and Turka, L. A., The complementary roles of deletion and regulation in transplantation tolerance. Nat. Rev. Immunol. 2003. 3: 147158.
  • 54
    Caillard, S., Dharnidharka, V., Agodoa, L., Bohen, E. and Abbott, K., Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 2005. 80: 12331243.
  • 55
    Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L. and Kuchroo, V. K., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006. 441: 235238.
  • 56
    Corry, R. J., Winn, H. J. and Russell, P. S., Primarily vascularized allografts of hearts in mice. The role of H-2D, H-2K, and non-H-2 antigens in rejection. Transplantation 1973. 16: 343350.