CD4+ regulatory T cells in solid organ transplantation

Current Opinion in Organ Transplantation

Volumn 15, Issue 6, 2010, Pages 757-764

  Issa, Fadi ^a   Wood, Kathryn J ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

rejection; tolerance; transplantation; Treg

Indexed keywords

BASILIXIMAB; BELATACEPT; CALCINEURIN INHIBITOR; CD 28 ANTAGONIST; CYTOKINE RECEPTOR ANTAGONIST; DACLIZUMAB; TACROLIMUS; UNCLASSIFIED DRUG;

CARDIAC GRAFT REJECTION; CD4+ T LYMPHOCYTE; CELL EXPANSION; CELL ISOLATION; CELL THERAPY; DRUG RESEARCH; DRUG SCREENING; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HEART TRANSPLANTATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; IN VITRO STUDY; IN VIVO STUDY; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE FUNCTION; MULTIPLE ORGAN FAILURE; NONHUMAN; ORGAN TRANSPLANTATION; REGULATORY T LYMPHOCYTE; REVIEW;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOSUPPRESSION; IMMUNOTHERAPY, ADOPTIVE; MICE; ORGAN TRANSPLANTATION; T-LYMPHOCYTES, REGULATORY;

EID: 78649639989     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e32834017ae     Document Type: Review

References (106)

1. Meier-Kriesche HU, Schold JD, Srinivas TR, 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; 4:378-383.
2. Taylor A L, Watson CJ, Bradley JA. Immunosuppressiveagents in solid organ transplantation: mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol 2005; 56:23-46.
3. Marcen R. Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs 2009; 69:2227-2243.
4. Wood KJ, Bushell AR, Jones ND. The discovery of immunological tolerance: now more than just a laboratory solution. J Immunol 2010; 184:3-4.
5. Calne RY. Prope tolerance: the future of organ transplantation-from the laboratory to the clinic. Transplantation 2004; 77:930-932.
6. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol 2003; 3:199-210.
7. Shevach EM. Fromvanillato 28flavors: multiplevarietiesofTregulatorycells. Immunity 2006; 25:195-201.
8. Issa F, Schiopu A, Wood KJ. Role of Tcells in graft rejection andtransplanta-tion tolerance. Expert Rev Clin Immunol 2010; 6:155-169.
9. Brunkow ME, Jeffery EW, Hjerrild KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001; 27:68-73.
10. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, poly-endocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by muta-tions of FOXP3. Nat Genet 2001; 27:20-21.
11. Josefowicz SZ, Rudensky A. Control of regulatory T cell lineage commitment and maintenance. Immunity 2009; 30:616-625.
12. Hori S, Nomura T, Sakaguchi S. Control of regulatoryT cell development by the transcription factor Foxp3. Science 2003; 299:1057-1061.
13. Karim M, Kingsley CI, Bushell AR, et al. Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25-CD4+ precursors in a thymus-independent process. J Immunol 2004; 172:923-928.
14. Kingsley CI, Karim M, Bushell A R, Wood KJ. CD25+CD4+ regulatoryTcells prevent graft rejection: CTLA-4-and IL-10-dependent immunoregulation of alloresponses. J Immunol 2002; 168:1080-1086.
15. Karim M, Feng G, Wood KJ, Bushell AR. CD25+CD4+ regulatory T cells generated by exposuretoa model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation. Blood 2005; 105:4871-4877.
16. Roncarolo MG, Gregori S, Battaglia M, et al. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev 2006; 212:28-50.
17. Kemper C, Chan AC, Green JM, et al. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 2003; 421:388-392.
18. Pillai V, Ortega SB, Wang CK, Karandikar NJ. Transient regulatory T-cells: a stateattained byall activated humanT-cells. Clin Immunol 2007; 123:18-29.
19. Wang J, Ioan-Facsinay A, van der Voort EI, et al. Transient expression of FOXP3 in human activated nonregulatoryCD4+Tcells. Eur J Immunol 2007; 37:129-138.
20. Lal G, Bromberg JS. Epigenetic mechanisms of regulation of Foxp3 expres-sion. Blood 2009; 114:3727-3735.
21. Lal G, Zhang N, van der Touw W, et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 2009; 182:259-273.
22. Wieczorek G, Asemissen A, Model F, et al. 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.
23. Thornton AM, Korty PE, Tran DQ, et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol 2010; 184:3433-3441.
24. Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppres-sion. Immunity 2009; 30:636-645.
25. Broere F, Wieten L, Klein Koerkamp EI, et al. Oral or nasal antigen induces regulatory T cells that suppress arthritis and proliferation of arthritogenic T cells in joint draining lymph nodes. J Immunol 2008; 181:899-906.
26. Wang L, Toda M, Saito K, et al. Postimmune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses. Int Immunol 2008; 20:57-70.
27. Ludwig-Portugall I, Hamilton-Williams EE, Gottschalk C, Kurts C. Cutting edge: CD25+ regulatory T cells prevent expansion and induce apoptosis of B cells specific fortissue autoantigens. J Immunol 2008; 181:4447-4451.
28. Vignali DA, Collison LW, Workman CJ. How regulatoryT cellswork. Nat Rev Immunol 2008; 8:523-532.
29. Gondek DC, Lu LF, Quezada SA, et al. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-de-pendent, perforin-independent mechanism. J Immunol 2005; 174:1783-1786.
30. Grossman WJ, Verbsky JW, Barchet W, et al. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004; 21:589-601.
31. Garin MI, Chu CC, Golshayan D, et al. Galectin-1: akeyeffectorof regulation mediated by CD4+CD25+ T cells. Blood 2007; 109:2058-2065.
32. Hara M, Kingsley CI, Niimi M, et al. IL-10 is required for regulatory T cells to media tetolerance toalloantigens invivo. J Immunol 2001; 166:3789-3796.
33. Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450:566-569.
34. Tang Q, Boden EK, Henriksen KJ, et al. Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function. Eur J Immunol 2004; 34:2996-3005.
35. Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells sup-press polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998; 188:287-296.
36. Pandiyan P, Zheng L, Ishihara S, et al. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol 2007; 8:1353-1362.
37. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008; 322:271-275.
38. Mellor AL, Munn DH. DO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4:762-774.
39. Liang B, Workman C, Lee J, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagementofMHCclass II. J Immunol 2008; 180:5916-5926.
40. Shalev I, Liu H, Koscik C, et al. Targeted deletion of fgl2 leads to impaired regulatoryTcell activity and developmentofautoimmune glomerulonephritis. J Immunol 2008; 180:249-260.
41. Borsellino G, Kleinewietfeld M, Di Mitri D, et al. Expression of ectonucleo-tidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immunesuppression. Blood 2007; 110:1225-1232.
42. Bushell A, Wood K. GITR ligation blocks allograft protection by induced CD25+CD4+ regulatory T cells without enhancing effector T-cell function. Am J Transplant 2007; 7:759-768.
43. Kitamura N, Murata S, Ueki T, et al. OX40 costimulation can abrogate Foxp3+ regulatory T cell-mediated suppression of antitumor immunity. Int J Cancer2009; 125:630-638.
44. Gri G, Piconese S, Frossi B, et al. CD4+CD25+ regulatory Tcells suppress mast cell degranulation and allergic responses through OX40-OX40L inter-action. Immunity2008; 29:771-781.
45. Piconese S, Gri G, Tripodo C, et al. Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation. Blood 2009; 114:2639-2648.
46. Griseri T, Asquith M, Thompson C, Powrie F. OX40 is required for regulatory T cell-mediated control of colitis. J Exp Med 2010; 207:699-709.
47. Ruby CE, Yates MA, Hirschhorn-Cymerman D, et al. Cutting edge: OX40 agonists can drive regulatoryT cell expansion if the cytokine milieu is right. J Immunol 2009; 183:4853-4857.
48. Zhou X, Bailey-Bucktrout SL, Jeker LT, et al. Instability of the transcription factorFoxp3 leadstothegeneration of pathogenicmemoryTcells invivo. Nat Immunol 2009; 10:1000-1007.
49. Yang XO, Nurieva R, Martinez GJ, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008; 29:44-56.
50. Komatsu N, Mariotti-Ferrandiz ME, Wang Y, et al. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci USA 2009; 106:1903-1908.
51. Duarte JH, Zelenay S, Bergman M-L, et al. Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopaenic conditions. Eur J Immunol 2009; 39:948-955.
52. Dijke IE, Velthuis JH, Caliskan K, et al. Intragraft FOXP3 mRNA expression reflects antidonor immune reactivity in cardiac allograft patients. Transplan-tation 2007; 83:1477-1484.
53. Bunnag S, Allanach K, Jhangri GS, et al. FOXP3 expression in human kidney transplant biopsies is associated with rejection and time post transplant but not with favorable outcomes. Am J Transplant 2008; 8:1423-1433.
54. Muthukumar T, Dadhania D, Ding R, et al. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N Engl J Med 2005; 353:2342-2351.
55. Carroll RP, Segundo D S, Hollowood K, et al. Immune phenotype predicts risk for posttransplantation squamous cell carcinoma. J Am Soc Nephrol 2010; 21:713-722.
56. Koshiba T, Li Y, Takemura M, et al. Clinical, immunological, and pathological aspects of operational tolerance after pediatric living-donor livertransplanta-tion. Transpl Immunol 2007; 17:94-97.
57. Li Y, Koshiba T, Yoshizawa A, et al. Analyses of peripheral blood mononuclear cells in operational tolerance after pediatric living donor livertransplantation. Am J Transplant 2004; 4:2118-2125.
58. Li Y, Zhao X, Cheng D, et al.The presenceofFoxp3 expressing Tcells within grafts of tolerance human liver transplant recipients. Transplantation 2008; 86:1837-1843.
59. Martinez-Llordella M, Puig-Pey I, Orlando G, et al. Multiparameter immune profiling of operational tolerance in liver transplantation. Am J Transplant 2007; 7:309-319.
60. Long E, Wood KJ. Regulatory T cells in transplantation: transferring mouse studies to the clinic. Transplantation 2009; 88:1050-1056.
61. Warnecke G, Bushell A, Nadig SN, Wood KJ. Regulation of transplant arteriosclerosis by CD25+CD4+ T cells generated to alloantigen in vivo. Transplantation 2007; 83:1459-1465.
62. Kingsley CI, Nadig SN, Wood KJ. Transplantation tolerance: lessons from experimental rodent models. Transpl Int 2007; 20:828-841.
63. Long ET, Baker S, Oliveira V, et al. Alpha-1,2-mannosidase and hence N-glycosylation are required for regulatory T cell migration and allograft toler-ance in mice. PLo S One 2010; 5:e8894.
64. Webster KE, Walters S, Kohler RE, et al. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J Exp Med 2009; 206:751-760.
65. Oliveira V, Sawitzki B, Chapman S, et al. 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; 38:1677-1688.
66. Feng G, Gao W, Strom T, et al. Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition ofTh17 responses and generation of functional Foxp3 regulatoryT cells. Eur J Immunol 2008; 38:2512-2527.
67. Feng G, Wood KJ, Bushell A. Interferon-gamma conditioning ex vivo gen-erates CD25+CD62L+Foxp3+ regulatory T cells that prevent allograft rejection: potential avenues for cellular therapy. Transplantation 2008; 86:578-589.
68. Warnecke G, Feng G, Goto R, et al. CD4+ regulatory T cells generated in vitro with IFN-7 and allogeneic APC inhibit transplant arteriosclerosis. Am J Pathol 2010; 177:464-472.
69. Wei B, Baker S, Wieckiewicz J, Wood KJ. IFN-7 triggered STAT1-PKB/AKT signalling pathway influencesthefunction of alloantigen reactive regulatoryT cells. Am J Transplant 2010; 10:69-80.
70. Wang R, Wan Q, Kozhaya L, et al. Identification of a regulatory Tcell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression. PLo S One 2008; 3:e2705.
71. Liu W, Putnam A L,Xu-Yu Z, et al.CD127expression inverselycorrelateswith Fox P3 and suppressive function of human CD4+ T reg cells. J Exp Med 2006; 203:1701-1711.
72. Seddiki N, Santner-Nanan B, Martinson J, et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 2006; 203:1693-1700.
73. Putnam A L, Brusko T M, Lee MR, et al. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 2009; 58:652-662.
74. Nadig SN, Wieckiewicz 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.
75. Kleinewietfeld M, Starke M, Di Mitri D, et al. CD49d provides access to 'untouched' human Foxp3+ Treg free of contaminating effector cells. Blood 2009; 113:827-836.
76. Miyara M,Yoshioka Y, Kitoh A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the Fox P3 transcription factor. Immunity 2009; 30:899-911.
77. Riley JL, June CH, Blazar BR. Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity 2009; 30:656-665.
78. Yamaguchi T, Hirota K, Nagahama K, et al. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 2007; 27:145-159.
79. Trzonkowski P, Bieniaszewska M, Juscinska J, et al. First-in-man clinical results of thetreatment of patientswith graftversus hostdiseasewith human ex vivo expanded CD4+CD25+CD127-T regulatory cells. Clin Immunol 2009; 133:22-26.
80. Sagoo P, Lombardi G, Lechler RI. Regulatory T cells as therapeutic cells. Curr Opin Organ Transplant 2008; 13:645-653.
81. Allan SE,Alstad AN, Merindol N, et al.Generation ofpotentand stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol Ther 2008; 16:194-202.
82. Peters JH, Hilbrands LB, Koenen HJ, Joosten I. Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(pos)CD25(high) T cells for immunotherapy. PLo S ONE 2008; 3:e2233.
83. Masteller EL, Warner MR, Tang Q, et al. Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J Immunol 2005; 175:3053-3059.
84. Jiang S, Tsang J, Game DS, et al.Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: potential reagents to promote donor-specific transplantation tolerance. Transplantation 2006; 82:1738-1743.
85. Wekerle T. T-regulatory cells-what relationship with immunosuppressive agents? Transplant Proc 2008; 40:S13-S16.
86. Vogtenhuber C, Bucher C, Highfill SL, et al. Constitutively active Stat5b in CD4+ T cells inhibits graft-versus-host disease lethality associated with increased regulatory T-cell potency and decreased T effector cell responses. Blood 2010; 116:466-474.
87. Burchill MA, Yang J, Vogtenhuber C, et al. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol 2007; 178:280-290.
88. Delgoffe GM, Kole TP, Zheng Y, et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009; 30:832-844.
89. Battaglia M, Stabilini A, Migliavacca B, et al. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006; 177:8338-8347.
90. Zeiser R, Leveson-Gower DB, Zambricki EA, et al. Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regula-tory T cells compared with conventional CD4+ T cells. Blood 2008; 111:453-462.
91. Battaglia M, Stabilini A, Draghici E, et al. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes 2006; 55:40-49.
92. Gao W, Lu Y, El Essawy B, et al. Contrasting effects of cyclosporine and rapamycin inde novogeneration ofalloantigen-specific regulatoryTcells. Am J Transplant 2007; 7:1722-1732.
93. Hendrikx T K, Velthuis J H, Klepper M, et al. Monotherapy rapamycin allows an increase of CD4 CD25 Fox P3 T cells in renal recipients. Transpl Int 2009; 22:884-891.
94. Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+Fox P3+ regulatoryTcells. Blood 2005; 105:4743-4748.
95. Bloom DD, Chang Z, Fechner J H, et al. CD4+CD25+ FOXP3+ regulatoryT cells increase de novo in kidney transplant patients after immunodepletion with Campath-1 H. Am J Transplant 2008; 8:793-802.
96. Trzonkowski P, Zilvetti M, Chapman S, et al. Homeostatic repopulation by CD28-CD8+ T cells in alemtuzumab-depleted kidney transplant recipients treated with reduce dimmunosuppression. Am J Transplant 2008;8:338-347.
97. Bluestone JA, Liu W, Yabu JM, et al. The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am J Transplant 2008; 8:2086-2096.
98. Presser D, Sester U, Mohrbach J, et al. Differential kinetics of effector and regulatoryT cells in patients on calcineurin inhibitor-based drug regimens. Kidney Int 2009; 76:557-566.
99. Ma A, Qi S, Wang Z, et al. Combined therapy of CD4(+)CD25(+) regulatory T cells with low-dose sirolimus, but not calcineurin inhibitors, preserves suppressive function of regulatory T cells and prolongs allograft survival in mice. Int Immunopharmacol 2009; 9:553-563.
100. Vlad G, Ho EK, Vasilescu ER, et al. Anti-CD25 treatment and FOXP3-positive regulatoryTcells in hearttransplantation.Transpl Immunol 2007; 18:13-21.
101. Caproni M, Torchia D, Antiga E, et al. The effects of tacrolimus ointment on regulatory T lymphocytes in atopic dermatitis. J Clin Immunol 2006; 26:370-375.
102. Poirier N, Azimzadeh AM, Zhang T, et al. Inducing CTLA-4-dependent immune regulation by selective CD28 blockade promotes regulatoryT cells in organ transplantation. Sci Transl Med 2010; 2:17ra10.
103. Roncarolo M G, Battaglia M. Regulatory T-cell immunotherapyfortoleranceto self antigens and alloantigens in humans. Nat Rev Immunol 2007; 7:585-598.
104. Allan SE, Broady R,Gregori S, et al.CD4+T-regulatorycells:towardtherapy for human diseases. Immunol Rev 2008; 223:391-421.
105. Di Ianni M, Falzetti F, Carotti A, et al. 51st ASH annual meeting. http://ash.confex.com/ash/2009/webprogram/Paper18555.html.
106. Carlson RH. Adoptive immunotherapy with Tregs' prevents GVHD in mis-matched transplants. Oncol Times 2010; 32:19-20.