Regulatory T cells in transplantation

Experimental Organ Transplantation

Volumn , Issue , 2013, Pages 389-419

  Pons, José A ^a   Revilla Nuin, Beatriz ^a   Baroja Mazo, Alberto ^a   Ramírez, Pablo ^a   Parrilla, Pascual ^a  

^a HOSPITAL UNIVERSITARIO VIRGEN DE LA ARRIXACA   (Spain)

Author keywords

Cell therapy cell therapy; FoxP3; Regulatory T cells; Tolerance; Transplantation

Indexed keywords

EID: 84895221794     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (190)

1. Afzali B, Lechler RI. and Hernandez-Fuentes MP. Allorecognition and the alloresponse: clinical implications. Tissue Antigens. 2007; 69: 545-556.
2. Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D, Burns EJ, Sherr DH, Weiner HL and Kuchroo VK. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat. Immunol. 2010; 11: 854-861.
3. Aquino-Dias EC, Joelsons G, da Silva DM, Berdichevski RH, Ribeiro AR, Veronese FJ, Goncalves LF and Manfro RC. Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function. Kidney Int. 2008; 73: 877-884.
4. Asano M, Toda M, Sakaguchi N and Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med.1996; 184: 387-396.
5. Ashton-Chess J, Dugast E, Colvin RB, Giral M, Foucher Y, Moreau A, Renaudin K, Braud C, Devys A, Brouard S and Soulillou JP. Regulatory, effector, and cytotoxic T cell profiles in long-term kidney transplant patients. J. Am. Soc. Nephrol. 2009; 20: 1113-1122.
6. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K and Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011; 331: 337-341.
7. Baan CC, Van der Mast BJ, Klepper M, Mol WM, Peeters AM, Korevaar SS, Balk AH and Weimar W. Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation. 2005; 80: 110- 117.
8. Bach JF and Chatenoud L. Tolerance to islet autoantigens in type 1 diabetes. Annu. Rev. Immunol. 2001;19: 131-161.
9. (+) conventional T cells. Eur. J. Immunol. 2007; 37: 2378-2389.
10. Barr ML. Photopheresis in transplantation: future research and directions. Transplant. Proc. 1998; 30: 2248-2250.
11. (+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J. Exp. Med. 2002; 195: 603-616.
12. Batsford S, Dickenmann M, Durmuller U, Hopfer H, Gudat F and Mihatsch M. Is monitoring of FOXP3 Treg cells in renal transplants during acute cellular rejection episodes useful? Clin. Nephrol. 2011; 75:101-106.
13. Battaglia M. Potential T regulatory cell therapy in transplantation: how far have we come and how far can we go? Transpl. Int. 2010; 23: 761-770.
14. Battaglia M, Gregori S, Bacchetta R and Roncarolo MG. Tr1 cells: from discovery to their clinical application. Semin. Immunol. 2006; 18: 120-127.
15. Battaglia M, Stabilini A, Draghici E, Gregori S, Mocchetti C, Bonifacio E and Roncarolo MG. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes. 2006; 55: 40-49.
16. Beeston T, Smith TR, Maricic I, Tang X and Kumar V. Involvement of IFN-gamma and perforin, but not Fas/FasL interactions in regulatory T cell-mediated suppression of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 2010; 229: 91-97.
17. Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat. Rev. Immunol. 2007; 7: 875-888.
18. Benson MJ, Pino-Lagos K, Rosemblatt M and Noelle RJ. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J. Exp. Med. 2007; 204: 1765-1774.
19. Bettelli E, Dastrange M and Oukka M. Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc. Natl. Acad. Sci. U S A. 2005; 102: 5138-5143.
20. + cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome. Transplantation. 2010; 90: 540-546.
21. Billingham RE, Brent L and Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953; 172: 603-606.
22. + regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am. J. Transplant. 2008; 8: 793-802.
23. Bopp T, Becker C, Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Heib V, Becker M, Kubach J, Schmitt S, Stoll S, Schild H, Staege MS, Stassen M, Jonuleit H. and Schmitt E. Cyclic adenosine monophosphate is a key component of regulatory T cellmediated suppression. J. Exp. Med. 2007; 204: 1303-1310.
24. + Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007; 110: 1225-1232.
25. Bour-Jordan H and Bluestone J.A. Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells. Immunol. Rev. 2009; 229: 41-66.
26. + T cells with normal immuno-regulatory properties in long-term graft outcome. Transpl. Int. 2007; 20: 845-855.
27. Broady R, Yu J and Levings MK. ATG-induced expression of FOXP3 in human CD4(+) T cells in vitro is associated with T-cell activation and not the induction of FOXP3(+) T regulatory cells. Blood. 2009; 114: 5003-5006.
28. Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF and Ramsdell F. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 2001; 27: 68-73.
29. Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR and Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011; 117: 1061-1070.
30. + regulatory T cells. Nat. Rev. Immunol. 2011;11: 119-130.
31. Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR and Ley TJ. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007; 27: 635-646.
32. Carvalho-Gaspar M, Jones ND, Luo S, Martin L, Brook, MO and Wood KJ. Location and time-dependent control of rejection by regulatory T cells culminates in a failure to generate memory T cells. J. Immunol. 2008; 180: 6640-6648.
33. + Treg Cells. J. Biol. Regul. Homeost. Agents. 2010; 24: 131-135.
34. +IL-7Ralphahigh cell population in solid organ transplant recipients. J. Exp. Med. 2007; 204: 1533-1541.
35. Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, Finkelstein D, Forbes K, Workman CJ, Brown SA, Rehg JE, Jones ML, Ni HT, Artis D, Turk MJ and Vignali DA. IL-35-mediated induction of a potent regulatory T cell population. Nat. Immunol. 2010; 11: 1093-1101.
36. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM., Cross R, Sehy D, Blumberg RS and Vignali DA. The inhibitory cytokine IL-35 contributes to regulatory Tcell function. Nature. 2007; 450: 566-569.
37. + regulatory T cells: more of the same or a division of labor? Immunity. 2009; 30: 626-635.
38. Chai JG, Xue SA, Coe D, Addey C, Bartok I, Scott D, Simpson E, Stauss HJ, Hori S, Sakaguchi S and Dyson J. Regulatory T cells, derived from naive CD4+CD25-T cells by in vitro Foxp3 gene transfer, can induce transplantation tolerance. Transplantation. 2005; 79: 1310-1316.
39. + regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 2003;198:1875-1886.
40. Chen X and Oppenheim JJ. The phenotypic and functional consequences of tumour necrosis factor receptor type 2 expression on CD4(+) FoxP3(+) regulatory T cells. Immunology. 2011; 133:426-433.
41. Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR and Howard OM. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur. J. Immunol. 2006; 36: 2139-2149.
42. + regulatory T cells. Int. Immunol. 2007; 19: 1003-1010.
43. Daniele N, Scerpa MC, Landi F, Caniglia M, Miele MJ, Locatelli F, Isacchi G. and Zinno F. T(reg) cells: collection, processing, storage and clinical use. Pathol. Res. Pract. 2011; 207: 209-215.
44. De Serres SA, Yeung MY, Mfarrej BG. and Najafian N. Effect of biologic agents on regulatory T cells. Transplant. Rev. (Orlando). 2011; 25: 110-116.
45. Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat., Chen, JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB and Robson SC. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 2007; 204: 1257-1265.
46. Degauque N, Mariat C, Kenny J, Zhang D, Gao W, Vu MD, Alexopoulos S, Oukka M, Umetsu DT, DeKruyff RH, Kuchroo V, Zheng XX and Strom TB. Immunostimulatory Tim-1-specific antibody deprograms Tregs and prevents transplant tolerance in mice. J. Clin. Invest. 2008; 118: 735-741.
47. Demirkiran A, Baan CC, Kok A, Metselaar HJ, Tilanus HW and van der Laan LJ. Intrahepatic detection of FOXP3 gene expression after liver transplantation using minimally invasive aspiration biopsy. Transplantation. 2007; 83: 819-823.
48. + regulatory T cells: does in vitro evidence translate to the clinical setting? Transplantation. 2008; 85: 783-789.
49. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F and Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011; 117: 3921-3928.
50. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Del Papa., Perruccio K, Ruggeri L, Sportoletti P, Rosati E, Marconi P, Falini B, Reisner Y, Velardi A, Aversa F and Martelli MF. Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation. Best Pract. Res. Clin. Haematol. 2011; 24: 459-466.
51. Dummer CD, Carpio VN, Goncalves LF, Manfro RC and Veronese FV. FOXP3(+) regulatory T cells: From suppression of rejection to induction of renal allograft tolerance. Transpl. Immunol. 2012; 26: 1-10.
52. Fadok VA, Bratton DL, Guthrie L and Henson PM. Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases. J. Immunol. 2001; 166: 6847-6854.
53. Fahlen L, Read S, Gorelik L, Hurst SD, Coffman RL, Flavell RA and Powrie F. T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J. Exp. Med. 2005; 201: 737-746.
54. Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML and Puccetti P. Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol. 2003; 4: 1206-1212.
55. Floess S, Freyer J, Siewert C, Baron U, Olek S, Polansky J, Schlawe K, Chang HD, Bopp T, Schmitt E, Klein-Hessling S, Serfling E, Hamann A and Huehn J. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007; 5: e38.
56. + regulatory T cells. Nat. Immunol. 2003; 4: 330-336.
57. Fontenot JD and Rudensky AY. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat. Immunol. 2005; 6: 331-337.
58. Fritzsching B, Oberle N, Pauly E, Geffers R, Buer J, Poschl J, Krammer P, Linderkamp O. and Suri-Payer E. Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death. Blood. 2006;108: 3371-3378.
59. + CD62+ T-regulatory cell subset has optimal suppressive and proliferative potential. Am. J. Transplant. 2004; 4: 65-78.
60. Gao W, Thompson L, Zhou Q, Putheti P, Fahmy TM, Strom TB and Metcalfe SM. Treg versus Th17 lymphocyte lineages are cross-regulated by LIF versus IL-6. Cell Cycle. 2009;8: 1444-1450.
61. + T cells. Blood. 2007; 109: 2058- 2065.
62. Gershon RK. and Kondo K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology. 1970; 18; 723-737.
63. Getnet D, Grosso JF, Goldberg MV, Harris TJ, Yen HR, Bruno TC, Durham NM, Hipkiss EL, Pyle KJ, Wada S, Pan F, Pardoll DM and Drake CG. A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol. Immunol. 2010; 47: 1595-1600.
64. Getnet D, Maris CH, Hipkiss EL, Grosso JF, Harris TJ, Yen HR, Bruno TC, Wada S, Adler A, Georgantas RW, Jie C, Goldberg MV, Pardoll DM and Drake CG. Tumor recognition andself-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells. J. Immunol. 2009; 182: 4675-4685.
65. Gregson AL, Hoji A, Palchevskiy V, Hu S, Weigt SS, Liao E, Derhovanessian A, Saggar R, Song S, Elashoff R, Yang OO. and Belperio JA. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells. PLoS One. 2010; 5: e11354.
66. Grohmann U, Orabona C, Fallarino F, Vacca C, Calcinaro F, Falorni A, Candeloro P, Belladonna, ML, Bianchi R, Fioretti MC and Puccetti P. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol. 2002; 3: 1097-1101.
67. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenk, S, de Vries JE. and Roncarolo MG. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997; 389: 737-742.
68. Hall BM, Verma ND, Tran GT and Hodgkinson SJ. Distinct regulatory CD4+T cell subsets; differences between naive and antigen specific T regulatory cells. Curr. Opin. Immunol. 2011; 23: 641-647.
69. Halloran PF, Bromberg J, Kaplan B and Vincenti F. Tolerance versus immunosuppression: a perspective. Am. J. Transplant. 2008; 8: 1365-1366.
70. Hamano K, Rawsthorne MA, Bushell AR, Morris PJ and Wood KJ. Evidence that the continued presence of the organ graft and not peripheral donor microchimerism is essential for maintenance of tolerance to alloantigen in vivo in anti-CD4 treated recipients. Transplantation. 1996; 62: 856-860.
71. Hammerich L, Heymann F and Tacke F. Role of IL-17 and Th17 cells in liver diseases. Clin. Dev. Immunol. 2011; 2011:345803.
72. Haque R, Lei F, Xiong X and Song J. The Regulation of FoxP3-Expressing Regulatory T Cells. Endocr. Metab. Immune Disord. Drug Targets. 2011.
73. Haxhinasto S, Mathis D and Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J. Exp. Med. 2008; 205: 565-574.
74. + T cells during acute rejection in liver transplant patients. Transplant. Proc. 2011; 43: 1696-1700.
75. Hendrikx TK, Velthuis JH, Klepper M, Van Gurp E, Geel A, Schoordijk W, Baan CC and Weimar W. Monotherapy rapamycin allows an increase of CD4 CD25 FoxP3 T cells in renal recipients. Transpl. Int. 2009; 22: 884-891.
76. Hippen KL, Riley JL, June CH and Blazar BR. Clinical perspectives for regulatory T cells in transplantation tolerance. Semin. Immunol. 2011; 23: 462-468.
77. Honkanen-Scott M, Johnson J, Hering B and Bansal-Pakala P. Blockade of OX40 signals enhance survival of xenoislet grafts in spontaneously diabetic NOD mice. Transplant. Proc. 2008; 40: 483-485.
78. Hori S, Nomura T and Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003; 299: 1057-1061.
79. Issa F and Wood KJ. CD4+ regulatory T cells in solid organ transplantation. Curr. Opin. Organ Transplant. 2010.
80. Iwase H, Kobayashi T, Kodera Y, Miwa Y, Kuzuya T, Iwasaki K, Haneda M, Katayama A, Takeda A, Morozumi K., Watarai Y, Uchida K and Nakao A. Clinical significance of regulatory T-cell-related gene expression in peripheral blood after renal transplantation. Transplantation. 2011; 91: 191-198.
81. + regulatory T cells in an IL-2-dependent manner. Transplantation 2008; 86: 1492-1502.
82. Kang SM, Tang Q and Bluestone JA. CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects. Am. J. Transplant. 2007; 7; 1457-1463.
83. Karagiannidis C, Akdis M, Holopainen P, Woolley NJ, Hense G, Ruckert B, Mantel PY, Menz G, Akdis CA, Blaser K and Schmidt-Weber CB. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J. Allergy Clin. Immunol. 2004; 114: 1425-1433.
84. + T regulatory cells. Nat. Immunol. 2003; 4: 337-342.
85. Kleinclauss F, Perruche S, Masson E, de Carvalho Bittencourt M, Biichle S, Remy-Martin JP, Ferrand C, Martin M, Bittard H, Chalopin JM, Seilles E, Tiberghien P and Saas P. Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory Tcell expansion. Cell Death Differ.2006; 13: 41-52.
86. + Treg free of contaminating effector cells. Blood. 2009; 113: 827-836.
87. + regulatory T cells. Proc. Natl. Acad. Sci. U S A. 2008; 105: 18460-18465.
88. Lal, G. and Bromberg, J.S. Epigenetic mechanisms of regulation of Foxp3 expression. Blood. 2009; 114: 3727-3735.
89. Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP, Reid SP, Levy DE and Bromberg JS. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J. Immunol. 2009;182: 259-273.
90. Li L and Boussiotis VA. Molecular and functional heterogeneity of T regulatory cells. Clin. Immunol. 2011;141: 244-252.
91. Li XC, and Turka LA. An update on regulatory T cells in transplant tolerance and rejection. Nat. Rev. Nephrol. 2010; 6: 577-583.
92. Li Y, Zhao X, Cheng D, Haga H, Tsuruyama T, Wood K, Sakaguchi S, Tanaka K, Uemoto S and Koshiba T. The presence of Foxp3 expressing T cells within grafts of tolerant human liver transplant recipients. Transplantation. 2008; 86: 1837-1843.
93. Liang B, Workman C, Lee J, Chew C, Dale BM, Colonna L, Flores M, Li N, Schweighoffer E, Greenberg S, Tybulewicz V, Vignali D and Clynes R. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J. Immunol. 2008; 180: 5916-5926.
94. + regulatory T cells. J. Immunol. 2005; 175: 4180-4183.
95. + T reg cells. J. Exp. Med. 2006; 203: 1701-1711.
96. + regulatory T cells. Nat. Immunol. 2008; 9: 632-640.
97. Lopes JE, Torgerson TR, Schubert, LA, Anover SD, Ocheltree EL, Ochs HD and Ziegler SF Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J. Immunol. 2006;177: 3133-3142.
98. Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S and Annunziato F. Thymic regulatory T cells. Autoimmun. Rev.2005; 4:579-586.
99. + regulatory T cells independent of autocrine TGF-beta1. Blood. 2004; 103: 4594-4601.
100. + regulatory T cells. J. Exp. Med. 2005; 201: 1061- 1067.
101. Martinez-Llordella M, Lozano JJ, Puig-Pey I, Orlando G, Tisone G, Lerut J, Benitez C, Pons JA, Parrilla, P, Ramirez P, Bruguera M, Rimola A and Sanchez-Fueyo A. Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients. J. Clin. Invest. 2008; 118; 2845-2857.
102. Martinez-Llordella M, Puig-Pey I, Orlando G, Ramoni M, Tisone G, Rimola, A, Lerut J, Latinne D, Margarit C, Bilbao I, Brouard S, Hernandez-Fuentes M, Soulillou JP and Sanchez-Fueyo A. Multiparameter immune profiling of operational tolerance in liver transplantation. Am. J. Transplant. 2007;7: 309-319.
103. Martinon F, Gaide O, Petrilli V, Mayor A and Tschopp J. NALP inflammasomes: a central role in innate immunity. Semin. Immunopathol. 2007; 29: 213-229.
104. Maruyama T, Konkel JE, Zamarron BF and Chen W. The molecular mechanisms of Foxp3 gene regulation. Semin. Immunol. 2011; 23: 418-423.
105. + and Foxp3-precursor cells in the absence of interleukin 10. Nat. Immunol. 2007;8: 931-941.
106. McGeachy MJ, Stephens LA and 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.
107. McMurchy AN, Bushell A, Levings MK and Wood KJ. Moving to tolerance: clinical application of T regulatory cells. Semin. Immunol. 2011;23: 304-313.
108. + regulatory T cells. J. Immunol. 2011;186: 4535-4540.
109. Merkenschlager M and Von Boehmer H. PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors. J. Exp. Med. 2010; 207: 1347-1350.
110. Mitchell P, Afzali B, Lombardi G and Lechler RI. The T helper 17-regulatory T cell axis in transplant rejection and tolerance. Curr. Opin. Organ Transplant. 2009;14: 326-331.
111. + T cells expressing the FoxP3 transcription factor. Immunity. 2009; 30: 899- 911.
112. Muller YD, Seebach JD, Buhler LH, Pascual M and Golshayan D. Transplantation tolerance: Clinical potential of regulatory T cells. Self Nonself. 2011; 2: 26-34.
113. Munn DH and Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest. 2007; 117: 1147-1154.
114. Muthukumar T, Dadhania D, Ding R, Snopkowski C, Naqvi R, Lee JB., Hartono C, Li B, Sharma VK, Seshan SV, Kapur S, Hancock WW, Schwartz JE and Suthanthiran M. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N. Engl. J. Med. 2005; 353: 2342-2351.
115. Nadig SN, Wieckiewicz J, Wu DC, Warnecke G, Zhang W, Luo S, Schiopu A, Taggart DP and Wood KJ. In vivo prevention of transplant arteriosclerosis by ex vivo-expanded human regulatory T cells. Nat. Med. 2010;16: 809-813.
116. Nakamura K, Kitani A and Strober W. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J. Exp. Med. 2001; 194: 629-644.
117. Nepom GT, St Clair EW and Turka LA. Challenges in the pursuit of immune tolerance. Immunol. Rev.2011; 241: 49-62.
118. Noris M, Casiraghi F, Todeschini M, Cravedi P, Cugini D, Monteferrante G, Aiello S, Cassis L, Gotti E, Gaspari F, Cattaneo D, Perico N and Remuzzi G. Regulatory T cells and T cell depletion: role of immunosuppressive drugs. J. Am. Soc. Nephrol. 2007; 18: 1007- 1018.
119. + regulatory T cells: independence of IL-2 consumption, TGF-beta, and various inhibitors of TCR signaling. J. Immunol. 2007; 179: 3578-3587.
120. + regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends Pharmacol. Sci. 2011; 32: 158-166.
121. + natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc. Natl. Acad. Sci. U S A. 2008; 105: 10113-10118.
122. Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T and Sakaguchi S. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature. 2007;446: 685-689.
123. Pallotta MT, Orabona C, Volpi C, Vacca C, Belladonna ML., Bianchi R, Servillo G, Brunacci, C, Calvitti M, Bicciato S, Mazza EM, Boon L, Grassi F, Fioretti MC, Fallarino F, Puccetti, P and Grohmann U. Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat. Immunol. 2011;12: 870-878.
124. + T cells. Nat. Immunol. 2007; 8: 1353-1362.
125. Paust S and Cantor H. Regulatory T cells and autoimmune disease. Immunol. Rev.2005; 204: 195-207.
126. + regulatory T cells responsible for protection against diabetes. Proc. Natl. Acad. Sci. U S A. 2004; 101: 4572-4577.
127. Perruche S, Zhang P, Liu Y, Saas P, Bluestone JA, and Chen W. CD3-specific antibodyinduced immune tolerance involves transforming growth factor-beta from phagocytes digesting apoptotic T cells. Nat. Med. 2008; 14: 528-535.
128. Pons JA, Revilla-Nuin B, Baroja-Mazo A, Ramirez P, Martinez-Alarcon L, Sanchez-Bueno F, Robles R, Rios A, Aparicio P and Parrilla P. FoxP3 in peripheral blood is associated with operational tolerance in liver transplant patients during immunosuppression withdrawal. Transplantation. 2008; 86: 1370-1378.
129. Pot C, Apetoh L, Awasthi A and Kuchroo VK. Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27. Semin. Immunol. 2011; 23: 438-445.
130. Riley JL., June CH and Blazar BR. Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity. 2009;30: 656-665.
131. + regulatory T cells at the single-cell level. Eur. J. Immunol. 2005; 35: 1681-1691.
132. Roncarolo MG and Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat. Rev. Immunol. 2007; 7: 585-598.
133. Rudensky AY. Regulatory T cells and Foxp3. Immunol. Rev.2011; 241: 260-268.
134. Sakaguchi S. The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 2003; 112: 1310-1312.
135. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 2005; 6: 345-352.
136. + regulatory T cells in the human immune system. Nat. Rev. Immunol. 2010;10: 490-500.
137. Sakaguchi S, Sakaguchi N, Asano N, Itoh M and 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. 1955; 155: 1151-1164.
138. Sakaguchi S, Yamaguchi T, Nomura T and Ono M. Regulatory T cells and immune tolerance. Cell. 2008; 133: 775-787.
139. Salcido-Ochoa F, Tsang J, Tam P, Falk K and Rotzschke O. Regulatory T cells in transplantation: does extracellular adenosine triphosphate metabolism through CD39 play a crucial role? Transplant. Rev. (Orlando).2010; 24: 52-66.
140. Samon JB, Champhekar A, Minter LM, Telfer JC, Miele L, Fauq A, Das P, Golde TE and Osborne BA. Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Blood. 2008; 112: 1813-1821.
141. San Segundo D, Ruiz JC, Fernandez-Fresnedo G, Izquierdo M, Gomez-Alamillo C, Cacho E, Benito MJ, Rodrigo E, Palomar R, Lopez-Hoyos M and Arias M. Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients. Transplant. Proc.2006; 38: 2391-2393.
142. Sanchez-Fueyo A and Strom TB. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology 2011; 140: 51- 64.
143. Shalev I, Schmelzle M, Robson SC and Levy G. Making sense of regulatory T cell suppressive function. Semin. Immunol. 2011; 23: 282-292.
144. + Treg cells correlate with transplant outcomes: a systematic review on recipients of solid organ transplantation. Cell Immunol. 2011; 270, 5-12.
145. Shevach EM. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity.2006; 25: 195-201.
146. + T regulatory cell-mediated suppression. Immunity. 2009; 30: 636-645.
147. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C, Ohta A and Thiel M. Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Annu. Rev. Immunol. 2004; 22: 657-682.
148. + T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J. Immunol. 2006;176: 1582-1587.
149. Strom TB and Koulmanda M. Recently discovered T cell subsets cannot keep their commitments. J. Am. Soc. Nephrol. 2009; 20: 1677-1680.
150. Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M, Saris CJ, O'Shea JJ and Hunter CA. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat. Immunol. 2007; 8: 1363-1371.
151. Su H, Longhi MS, Wang P, Vergani D and Ma Y. Human CD4+CD25(high)CD127 (low/neg) Regulatory T Cells. Methods Mol. Biol. 2012; 806: 287-299.
152. + natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 2006; 18: 1197-1209.
153. + naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 1998; 10: 1969-1980.
154. + regulatory T cell: a jack of all trades, master of regulation. Nat. Immunol.2008; 9: 239-244.
155. Teft WA, Kirchhof MG and Madrenas J. A molecular perspective of CTLA-4 function. Annu. Rev. Immunol. 2006; 24: 65-97.
156. + T regulatory cells. J. Immunol. 2010; 184: 3433-3441.
157. + immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998; 188: 287-296.
158. Tone Y, Furuuchi K, Kojima Y, Tykocinski ML, Greene MI and Tone M. Smad 3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat. Immunol. 2008; 9: 194- 202.
159. + regulatory T cells allows for their purification from expansion cultures. Blood. 2009; 113: 5125-5133.
160. Trzonkowski P, Bieniaszewska M, Juscinska J, Dobyszuk A, Krzystyniak A, Marek N, Mysliwska J and Hellmann A. 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.
161. Urbani L, Mazzoni A, Colombatto P, Biancofiore G, Bindi L, Tascini C, Menichetti F, Brunetto M, Scatena F and Filipponi F. Potential applications of extracorporeal photopheresis in liver transplantation. Transplant. Proc.2008; 40: 1175-1178.
162. Vignali DA, Collison LW and Workman CJ. How regulatory T cells work. Nat. Rev. Immunol. 2008; 8: 523-532.
163. Vincenti F, Blancho G, Durrbach A, Friend P, Grinyo J, Halloran PF, Klempnauer J, Lang P, Larsen CP, Muhlbacher F, Nashan B, Soulillou JP, Vanrenterghem Y, Wekerle T, Agarwal M, Gujrathi S, Shen J, Shi R, Townsend R and Charpentier B. Five-year safety and efficacy of belatacept in renal transplantation. J. Am. Soc. Nephrol. 2010; 21: 1587- 1596.
164. Von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat. Immunol. 2005; 6: 338-344.
165. + Tregs. Blood. 2007; 110: 2501-2510.
166. Waldmann H. Tolerance: an overview and perspectives. Nat Rev Nephrol. 2010; 6:569-576.
167. - T cells. J. Clin. Invest. 2003; 112: 1437-1443.
168. Wan YY and Flavell RA. Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc. Natl. Acad. Sci. U S A. 2005; 102: 5126-5131.
169. Wang HY and Wang RF. Regulatory T cells and cancer. Curr. Opin. Immunol. 2007;19: 217- 223.
170. Weaver CT and Hatton RD. Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat. Rev. Immunol. 2009; 9: 883-889.
171. Weiner HL. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol. Rev.2001; 182: 207-214.
172. Wekerle T, Kurtz J, Bigenzahn S, Takeuchi Y and Sykes M. Mechanisms of transplant tolerance induction using costimulatory blockade. Curr. Opin. Immunol. 2002; 14: 592- 600.
173. Wieckiewicz J, Goto R and Wood KJ. T regulatory cells and the control of alloimmunity: from characterisation to clinical application. Curr. Opin. Immunol. 2010; 22: 662-668.
174. Wieczorek G, Asemissen A, Model F, Turbachova I, Floess S, Liebenberg V, Baron U, Stauch D, Kotsch K, Pratschke J, Hamann A, Loddenkemper C, Stein H, Volk HD, Hoffmuller U, Grutzkau A, Mustea A, Huehn J, Scheibenbogen C and Olek S. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res. 2009; 69: 599-608.
175. Wildin RS, Smyk-Pearson S and Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J. Med. Genet. 2002; 39: 537-545.
176. Wood KJ. Regulatory T cells in transplantation. Transplant. Proc. 2011; 43: 2135-2136.
177. Wood KJ, Bushell A and Jones ND. Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells. Immunol. Rev. 2011;241: 119-132.
178. Xia CQ, Campbell KA and Clare-Salzler MJ. Extracorporeal photopheresis-induced immune tolerance: a focus on modulation of antigen-presenting cells and induction of regulatory T cells by apoptotic cells. Curr. Opin. Organ Transplant. 2009; 14: 338-343.
179. Yamaguchi T, Wing JB and Sakaguchi S. Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions. Semin. Immunol. 2011; 23: 424-430.
180. Yokosuka T, Kobayashi W, Takamatsu M, Sakata-Sogawa K, Zeng H, Hashimoto-Tane A, Yagita H, Tokunaga M and Saito T. Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation. Immunity. 2010;33: 326-339.
181. Yong Z, Chang L, Mei YX and Yi L. Role and mechanisms of CD4+CD25+ regulatory T cells in the induction and maintenance of transplantation tolerance. Transpl. Immunol. 2007;17: 120-129.
182. Yu A, Zhu L, Altman NH and Malek TR. A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells. Immunity. 2009; 30: 204-217.
183. + regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006;108: 390-399.
184. Zhang C, Shan J, Feng L, Lu J, Xiao Z, Luo L, Li C, Guo,Y and Li Y. The effects of immunosuppressive drugs on CD4(+) CD25(+) regulatory T cells: a systematic review of clinical and basic research. J. Evid. Based Med. 2010;3: 117-129.
185. - cells to develop suppressive activity: the role of IL-2, TGFbeta, and IL-10. J. Immunol. 2004; 172: 5213-5221.
186. + regulatory cells. J. Immunol.2006; 176: 3321-3329.
187. Zheng, XX, Sanchez-Fueyo A, Domenig C and Strom T.B. The balance of deletion and regulation in allograft tolerance. Immunol. Rev. 2003;196: 75-84.
188. Zhou X, Bailey-Bucktrout, SL, Jeker LT, Penaranda C, Martinez-Llordella M, Ashby M, Nakayama M, Rosenthal W and Bluestone JA. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol.2009; 10: 1000-1007.
189. Ziegler SF. FOXP3: of mice and men. Annu. Rev. Immunol. 2006; 24: 209-226.
190. Ziegler SF. FOXP3: not just for regulatory T cells anymore. Eur. J. Immunol. 2007; 37: 21- 23.