1. Ehrlich P. Collected papers of Paul Ehrlich – vol. 2. New York: Pergamon 1957.
2. Burnet FM. The Clonal Selection Theory of Acquired Immunity. Cambridge: Cambridge University Press 1959.
3. Ivanyi J. Milan Hasek and the discovery of immunological tolerance. Nat Rev Immunol 2003; 3: 591–597.
4. Nossal GJ. Clonal anergy of B cells: a flexible, reversible, and quantitative concept. J Exp Med 1996; 183: 1953–56.
5. Sakaguchi S, Wing K, Miyara M. Regulatory T cells – a brief history and perspective. Eur J Immunol 2007; (Suppl. 1) 37: S116–123.
6. Gershon RK, Kondo K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 1970; 18: 723–737.
7. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 1151–1164.
8. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299: 1057–1061.
9. Singh B, Read S, Asseman C et al. Control of intestinal inflammation by regulatory T cells. Immunol Rev 2001; 182: 190–200.
10. Feng S. Long-term management of immunosuppression after pediatric liver transplantation: is minimization or withdrawal desirable or possible or both? Curr Opin Organ Transplant 2008; 13: 506–512.
11. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol 2003; 3: 199–210.
12. Bluestone JA, Tang Q. Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells Proc Natl Acad Sci USA 01 2004; (Suppl 2): 14622–14626.
13. Waldmann H, Adams E, Fairchild P, Cobbold S. Regulation and privilege in transplantation tolerance. J Clin Immunol 2008; 28: 716–725.
14. Trzonkowski P, Bieniaszewska M, Juscinska J, Dobyszuk A, Krzystyniak A, Marek N, et al. First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells. Clin Immunol 2009; 133: 22–26.
15. Brunstein CG, Miller JS, Cao Q, McKen DH., Hippen KL, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 2010; 117: 1061–1070.
16. Di Ianni M, Falzetti F, Carrotti A, Terenzi A, Castellino F, Bonifacio E, et al. Tregs prevent GvHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 2011; 117: 3921–3928.
17. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2001; 299: 1057–1061.
18. Khattri R., Cox T, Yasako S, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory T cells. Nat Immunol 2003; 4: 337–342.
19. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4: 330–336.
20. Gambieri E, Torgerson T, Ochs H. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic immunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003; 15: 430–435.
21. Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. J Med Genet 2002; 39: 537–545.
22. Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, 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 tolerance. J Immunol 1999; 162: 5317–5326.
23. Miyara M, Yoshioka Y, Kitoh A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009; 30: 899–911.
24. Danke NA, Koelle DM, Yee C, et al Autoreactive T cells in healthy individuals. J Immunol 2004; 172: 5967–5972.
25. Wing K, Lindgren S, Kollberg G, et al. CD4 T cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T cells. Eur J Immunol 2003; 33: 579–587.
26. Gnjatic S, Altorki NK, Tang DN, et al. NY-ESO-1 DNA vaccine induces T-cell responses that are suppressed by regulatory T cells. Clin Cancer Res 2009; 15: 2130–2139.
27. Danke NA, Yang J, Greenbaum C, Kwok WW. Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. J Autoimmun 2005; 25: 303-311.
28. Yang J, Danke N, Roti M, et al. CD4+ T cells from type 1 diabetic and healthy subjects exhibit different thresholds of activation to a naturally processed proinsulin epitope. J Autoimmun 2008; 31: 30–41.
29. Baxter AG. The origin and application of experimental autoimmune encephalomyelitis. Nat Rev Immunol 2007; 7: 904–912.
30. Scott DL, Wolfe F, Huizinga TW. Rheumatoid Arthritis. Lancet 2010; 376: 1094–1108.
31. Partlett R, Roussou E. The treatment of rheumatoid arthritis during pregnancy. Rheumatol Intl 2011; 31: 445–449.
32. de Man YA, Dolhain RJ, van de Geijn FE, et al. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum 2008; 59: 1241–1248.
33. Hench PS. The ameliorating effect of pregnancy on chronic atrophic (infectious rheumatoid) arthritis, fibrosis, and intermittent hydrarthrosis. Mayo Clin Proc 1938; 13: 161–167.
34. Golding A, Hague UJ, Giles JT. Rheumatoid arthritis and reproduction. Rheum Dis Clin North Am 2007; 33: 319–343.
35. Kallikourdis M, Andersen KG, Welch KA, Betz AG. Alloantigen-enhanced accumulation of CCR5+ ‘effector’ regulatory T cells in the gravid uterus. Proc Natl Acad Sci USA 2007; 104: 594–599.
36. Kahn DA, Baltimore D. Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance. Proc Natl Acad Sci USA 2010; 107: 9299–9304.
37. Munoz-Suano A, Kallikourdis M, Sarris M, Betz AG. Regulatory T cells protect from autoimmune arthritis during pregnancy. J Autoimmun 2012; 38: 103–108.
38. Zaccone P, Fehérvári Z, Blanchard L, et al. Autoimmune thyroid disease induced by thyroglobulin and lipopolysaccharide is inhibited by soluble TNF receptor type I. Eur J Immunol 2002; 32: 1021–1028.
39. Eriksson U, Ricci R, Hunziker L, Kurrer MO, Oudit GY, Watts TH. et al. Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat Med 2003; 9: 1484–1490.
40. Watanabe H, Inaba M, Adachi Y, Sugiura K, Hisha H, Iguchi T, et al. Experimental autoimmune thyroiditis induced by thyroglobulin-pulsed dendritic cells. Autoimmunity 1999; 31: 273–282.
41. Gehring AJ, Rojas RE, Canaday DH, et al. The mycobacterium tuberculosis 19-kilodalton lipoprotein inhibits gamma interferon-regulated HLA-DR and Fc gamma R1 on human macrophages through Toll-like receptor 2. Infect Immun 2003; 71: 4487–4497.
42. McGeachy MJ, Stephens LA, Anderton SM. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. J Immunol 2005; 175: 3025–3032.
43. Kohm AP, Carpenter PA, Anger HA, Miller SD. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 2002; 169: 4712–4716.
44. Morris GP, Yan Y, David CS, Kong YM. H2A- and H2E-derived CD4+CD25+ regulatory T cells: a potential role in reciprocal inhibition by class II genes in autoimmune thyroiditis. J Immunol 2005; 174: 3111–3116.
45. Reddy J, et al. Myelin proteolipid protein-specific CD4+CD25+ regulatory T cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2004; 101: 15434–15439.
46. Vaeth M, Gogishvili T, Bopp T, et al. Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1). Proc Natl Acad Sci USA 2011; 108: 2480–2485.
47. Bopp T, Becker C, Klein M, et al. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J Exp Med 2007; 204: 1303–1310.
48. Bodor J, Bopp T, Vaeth M, et al. Cyclic AMP underpins suppression by regulatory T cells. Eur J Immunol 2012; 42: 1375–1384.
49. Becker C, Bopp T, Jonuleit H. Boosting regulatory T cell function by CD4 stimulation enters the clinic. Front Immunol 2012; 3: 1–9.
50. Shevach EM. Mechanisms of Foxp3+ T regulatory cell-mediated suppression. Immunity 2009; 30: 636–645.
51. Vignali DAA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008; 8: 523–532.
52. Tang Q, Bluestone J. The Foxp3+ regulatory T cell: jack of all trades, master of regulation. Nat Immunol 2008; 9: 239–244.
53. Takahashi T, Tagami T, Yamazaki S, 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: 303–310.
54. Read S, Malstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays and essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J Exp Med 2000; 192: 295–302.
55. Peggs KS, Quezada SA, Chambers CA, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 2009; 206: 1717–1725.
56. Vendetti S, Riccomi A, Sacchi A, et al. Cyclic adenosine 5’-monophosphate and calcium induce CD152 (CTLA-4) up-regulation in resting CD4+ T lymphocytes. J Immunol 2002; 169: 6231–6235.
57. Bodor J, Fehervari Z, Diamond B, Sakaguchi S. ICER/CREM-mediated transcriptional attenuation of IL-2 and its role in suppression by regulatory T cells. Eur J Immunol 2007; 37: 884–895.
58. Lone AM, Tasken K. Proinflammatory and immunoregulatory roles of eicosanoids in T cells. Front Immunol 2013; 4: 1–15.
59. Medawar PB. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp Soc Exp Biol 1953; 7: 320–338.
60. Erlebacher A, Vencato D, Price KA, et al. Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus. J Clin Invest 2007; 117: 1399–1411.
61. Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 2012; 490: 102–106.
62. Bizargity P, Bonney EA. Dendritic cells, a family portrait at mid-gestation. Immunology 2009; 126: 565–578.
63. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012; 30: 531–564.
64. Josefowicz SZ, Niec RE, Kim HY, et al. Extrathymically generated regulatory T cells control mucosal Th2 inflammation. Nature 2012; 482: 395–399.
65. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nature Immunol 2004; 5: 266–271.
66. Zenclussen AC, Gerlof K, Zenclussen ML, et al. Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface. Eur J Immunol 2006; 36: 82–94.
67. Mjosberg J, Berg G, Jenmalm MC, Ernerudh J. FOXP3+ regulatory T cells and T helper 1, T helper 2 and T helper 17 cells in human early pregnancy decidua. Biol Reprod 2010; 82: 698–705.
68. Dimova T, Nagaeva O, Stenqvist AC, et al. Maternal Foxp3 expressing CD4+CD25+ and CD4+CD25- regulatory T cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. Am J Reprod Immunol 2011; 66 (Suppl. 1): 44–56.
69. Davies JD, O'Connor E, Hall D, et al. CD4+CD45RB low-density cells from untreated mice prevent acute allograft reaction. J Immunol 1999; 163: 5353–5357.
70. Taylor PA, Noelle RJ, Blazar BR. CD4+CD25+ immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade. J Exp Med 2001; 193: 1311–1318.
71. Earle KE, Tang Q, Zhou X, et al. In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation. Clin Immunol 2005; 115: 3–9.
72. Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4+CD25+ immunoregulatory T cells: new therapeutics for graft-versus-host disease. J Exp Med 2002; 196: 401–406.
73. Benghiat FS, Graca L, Braun MY, Detienne S, Moore F, Buonocore S, et al. Critical Influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression. Transplantation 2005; 79: 648–654.
74. Bolton EM. Regulatory T cells in transplantation: natural or induced? Transplantation 2005; 79: 643–645.
75. Lin YJ, Hara H, Tai HC, et al. Suppressive efficacy and proliferative capacity of human regulatory T cells in allogeneic and xenogeneic responses. Transplantation 2008; 86: 1452–1462.
76. Wise MP, Bemelman F, Cobbold SP, Waldmann H. Linked suppression of skin graft rejection can operate through indirect recognition. J Immunol 1998; 161: 5813–5816.
77. Ochando JC, Homma C, Yang Y, et al. Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat Immunol 2006; 7: 652–662.
78. Verginis P, McLaughlin KA, Wucherpfennig KW, et al. Induction of antigen-specific regulatory T cells in wild type mice: visualization and targets of suppression. Proc Natl Acad Sci USA 2008; 105: 3479–3484.
79. Hara M, Kingsley CI, Niimi M, et al. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J Immunol 2001; 166: 3789–3796.
80. Yamada A, Chandraker A, Laufer TM, et al. Recipient MHC class II expression is required to achieve long-term survival of murine cardiac allografts after costimulatory blockade. J Immunol 2001; 167: 5522–5526.
81. Callaghan CJ, Rouhani FJ, Negus MC., et al. Abrogation of antibody-mediated allograft rejection by regulatory CD4 T cells with indirect allospecificity. J Immunol 2007; 178: 2221–2228.
82. Nadig SN, Wieckekiewicz J, Wu DC, et al. In vivo prevention of transplant arteriosclerosis by ex vivo-expanded human regulatory T cells. Nat Med 2010; 16: 809–813.
83. Brennan TV, Tang Q, Liu FC, et al. Requirements for prolongation of allograft survival with regulatory T cell infusion in lymphosufficient hosts. J Surg Res 2011; 169: e69–75.
84. Sagoo P, Ali N, Garg G, Nestle FO, et al. Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells. Sci Transl Med 2011; 3: 83ra42.
85. Joffre O, Santolaria T, Calise D, et al. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat Med 2008; 14: 88–92.
86. Tsang JY, Tanriver Y, Jiang S, et al. Conferring indirect allospecificity on CD4+CD25+ Tregs by TCRT gene transfer favors transplantation tolerance in mice. J Clin Invest 2008; 118: 3619–3628.
87. Trzonkowski P, Zilvetti M, Friend P, Wood KJ. Recipient memory-like lymphocytes remain unresponsive to graft antigens after CAMPATH-1H induction with reduced maintenance immunosuppression. Transplantation 2006; 82: 1342–1351.
88. Pearl JP, Parris J, Hale DA., et al. Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant 2005; 5: 465–474.
89. Bloom DD, Chang Z, Fechner JH, et al. CD4+CD25+FOXP3+ regulatory T cells increase de novo in kidney transplant patients after immunodepletion with campath-1H. Am J Transplant 2008; 8: 793–802.
90. Lopez M, Clarkson MR, Albin M, et al. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol 2006; 17: 2844–2853.
91. Hester J, Schiopu A, Nadig SN, Wood KJ. Low dose of rapamycin treatment increases the ability of human regulatory T cells to inhibit transplant arteriosclerosis in vivo. Am J Transplant 2012; 12: 2008–2016.
92. Shin HJ, Baker J, Leveson-Gower DB, et al Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells. Blood 2011; 118: 2342–2350.
93. Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med 2011; 365: 2055–2066.