Transplantation tolerance

Pediatric Nephrology

Volumn 29, Issue 12, 2014, Pages 2263-2272

  Salisbury, Emma M ^a   Game, David S ^b   Lechler, Robert I ^c  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b GUY S HOSPITAL   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Allograft; Immunosuppression; Kidney; Tolerance; Transplant

Indexed keywords

EID: 84886969558     PISSN: 0931041X     EISSN: 1432198X     Source Type: Journal    
DOI: 10.1007/s00467-013-2659-5     Document Type: Review

References (86)

1. Billingham RE, Brent L, Medawar PB (1953) Actively acquired tolerance of foreign cells. Nature 172:603–606
2. Feng S, Ekong UD, Lobritto SJ, Demetris AJ, Roberts JP, Rosenthal P, Alonso EM, Philogene MC, Ikle D, Poole KM, Bridges ND, Turka LA, Tchao NK (2012) Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants. JAMA 307:283–293
3. Levitsky J (2011) Operational tolerance: past lessons and future prospects. Liver transplantation 17:222–232
4. Ramos HC, Reyes J, Abu-Elmagd K, Zeevi A, Reinsmoen N, Tzakis A, Demetris AJ, Fung JJ, Flynn B, McMichael J, Ebert F, Starzl TE (1995) Weaning of immunosuppression in long-term liver transplant recipients. Transplantation 59:212–217
5. Takatsuki M, Uemoto S, Inomata Y, Egawa H, Kiuchi T, Fujita S, Hayashi M, Kanematsu T, Tanaka K (2001) Weaning of immunosuppression in living donor liver transplant recipients. Transplantation 72:449–454
6. Brouard S, Dupont A, Giral M, Louis S, Lair D, Braudeau C, Degauque N, Moizant F, Pallier A, Ruiz C, Guillet M, Laplaud D, Soulillou JP (2005) Operationally tolerant and minimally immunosuppressed kidney recipients display strongly altered blood T-cell clonal regulation. Am J Transplant 5:330–340
7. Brouard S, Mansfield E, Braud C, Li L, Giral M, Hsieh SC, Baeten D, Zhang M, Ashton-Chess J, Braudeau C, Hsieh F, Dupont A, Pallier A, Moreau A, Louis S, Ruiz C, Salvatierra O, Soulillou JP, Sarwal M (2007) Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Proc Natl Acad Sci U S A 104:15448–15453
8. Leventhal J, Abecassis M, Miller J, Gallon L, Tollerud D, Elliott MJ, Bozulic LD, Houston C, Sustento-Reodica N, Ildstad ST (2013) Tolerance induction in HLA disparate living donor kidney transplantation by donor stem cell infusion: durable chimerism predicts outcome. Transplantation 95:169–176
9. Turka LA, Lechler RI (2009) Towards the identification of biomarkers of transplantation tolerance. Nat Rev Immunol 9:521–526
10. Afzali B, Lechler RI, Hernandez-Fuentes MP (2007) Allorecognition and the alloresponse: clinical implications. Tissue Antigens 69:545–556
11. Mengel M, Sis B, Haas M, Colvin RB, Halloran PF, Racusen LC, Solez K, Cendales L, Demetris AJ, Drachenberg CB, Farver CF, Rodriguez ER, Wallace WD, Glotz D, Banff meeting report writing committee (2012) Banff 2011 Meeting report: new concepts in antibody-mediated rejection. Am J Transplant 12:563–570
12. Lamb KE, Lodhi S, Meier-Kriesche HU (2011) Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant 11:450–462
13. Lodhi SA, Lamb KE, Meier-Kriesche HU (2011) Solid organ allograft survival improvement in the United States: the long-term does not mirror the dramatic short-term success. Am J Transplant 11:1226–1235
14. Newell KA, Phippard D, Turka LA (2011) Regulatory cells and cell signatures in clinical transplantation tolerance. Curr Opin Immunol 23:655–659
15. Caton AJ, Cozzo C, Larkin J 3rd, Lerman MA, Boesteanu A, Jordan MS (2004) CD4(+) CD25(+) regulatory T cell selection. Ann N Y Acad Sci 1029:101–114
16. Alferink J, Tafuri A, Vestweber D, Hallmann R, Hammerling GJ, Arnold B (1998) Control of neonatal tolerance to tissue antigens by peripheral T cell trafficking. Science 282:1338–1341
17. Zinkernagel RM (1996) Immunology taught by viruses. Science 271:173–178
18. Kurts C, Miller JF, Subramaniam RM, Carbone FR, Heath WR (1998) Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction. J Exp Med 188:409–414
19. Sykes M (2007) Immune tolerance: mechanisms and application in clinical transplantation. J Intern Med 262:288–310
20. Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME (2001) X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27:18–20
21. - precursors. J Immunol 169:4183–4189
22. Isomura I, Palmer S, Grumont RJ, Bunting K, Hoyne G, Wilkinson N, Banerjee A, Proietto A, Gugasyan R, Li W, McNally A, Steptoe RJ, Thomas R, Shannon MF, Gerondakis S (2009) c-Rel is required for the development of thymic Foxp3(+) CD4 regulatory T cells. J Exp Med 206:3001–3014
23. + regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886
24. Yang J, Brook MO, Carvalho-Gaspar M, Zhang J, Ramon HE, Sayegh MH, Wood KJ, Turka LA, Jones ND (2007) Allograft rejection mediated by memory T cells is resistant to regulation. Proc Natl Acad Sci U S A 104:19954–19959
25. Francis RS, Feng G, Tha-In T, Lyons IS, Wood KJ, Bushell A (2011) Induction of transplantation tolerance converts potential effector T cells into graft-protective regulatory T cells. Eur J Immunol 41:726–738
26. Wood KJ, Bushell A, Jones ND (2011) Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells. Immunol Rev 241:119–132
27. Graca L, Thompson S, Lin CY, Adams E, Cobbold SP, Waldmann H (2002) Both CD4(+)CD25(+) and CD4(+)CD25(−) regulatory cells mediate dominant transplantation tolerance. J Immunol 168:5558–5565
28. Feng G, Nadig SN, Backdahl L, Beck S, Francis RS, Schiopu A, Whatcott A, Wood KJ, Bushell A (2011) Functional regulatory T cells produced by inhibiting cyclic nucleotide phosphodiesterase type 3 prevent allograft rejection. Sci Transl Med 3:83ra40
29. + regulatory T cells that prevent allograft rejection: potential avenues for cellular therapy. Transplantation 86:578–589
30. Page EK, Dar WA, Knechtle SJ (2012) Tolerogenic therapies in transplantation. Front Immunol 3:198
31. Page E, Kwun J, Oh B, Knechtle S (2013) Lymphodepletional strategies in transplantation. Cold Spring Harb Perspect Med 3:pii: a015511
32. Wu H, Noordmans GA, O’Brien MR, Ma J, Zhao CY, Zhang GY, Kwan TK, Alexander SI, Chadban SJ (2012) Absence of MyD88 signaling induces donor-specific kidney allograft tolerance. J Am Soc Nephrol 23:1701–1716
33. Orlando G, Hematti P, Stratta RJ, Burke GW, Di Cocco P, Pisani F, Soker S, Wood K (2010) Clinical operational tolerance after renal transplantation: current status and future challenges. Ann Surg 252:915–928
34. Hall BM, Pearce NW, Gurley KE, Dorsch SE (1990) Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. 3. Further characterization of the CD4+ suppressor-cell and its mechanisms of action. J Exp Med 171:141–157
35. + T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389:737–742
36. Faria AM, Weiner HL (2005) Oral tolerance. Immunol Rev 206:232–259
37. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–569
38. + T suppressor cells and the ILT3 master switch. Hum Immunol 69:681–686
39. Zhang ZX, Yang L, Young KJ, DuTemple B, Zhang L (2000) Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat Med 6:782–789
40. Seino KI, Fukao K, Muramoto K, Yanagisawa K, Takada Y, Kakuta S, Iwakura Y, Van Kaer L, Takeda K, Nakayama T, Taniguchi M, Bashuda H, Yagita H, Okumura K (2001) Requirement for natural killer T (NKT) cells in the induction of allograft tolerance. Proc Natl Acad Sci U S A 98:2577–2581
41. Mauri C, Bosma A (2012) Immune regulatory function of B cells. Annu Rev Immunol 30:221–241
42. + regulatory T lymphocytes. Nat Med 14:88–92
43. + regulatory T cells promote experimental transplantation tolerance. Blood 109:827–835
44. Tsang JY, Tanriver Y, Jiang S, Leung E, Ratnasothy K, Lombardi G, Lechler R (2009) Indefinite mouse heart allograft survival in recipient treated with CD4(+)CD25(+) regulatory T cells with indirect allospecificity and short term immunosuppression. Transpl Immunol 21:203–209
45. Sagoo P, Ali N, Garg G, Nestle FO, Lechler RI, Lombardi G (2011) Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells. Sci Transl Med 3:83ra42
46. Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE (2011) Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 117:1061–1070
47. Edinger M, Hoffmann P (2011) Regulatory T cells in stem cell transplantation: strategies and first clinical experiences. Curr Opin Immunol 23:679–684
48. 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, Martelli MF (2011) Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 117:3921–3928
49. Li Y, Li XC, Zheng XX, Wells AD, Turka LA, Strom TB (1999) Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat Med 5:1298–1302
50. + regulatory T cells. Blood 105:4743–4748
51. Xu H, Ildstad ST (2012) Transplantation: is donor T-cell engraftment a biomarker for tolerance? Nat Rev Nephrol 8:560–561
52. Ildstad ST, Sachs DH (1984) Reconstitution with syngeneic plus allogeneic or xenogeneic bone-marrow leads to specific acceptance of allografts or xenografts. Nature 307:168–170
53. Kawai T, Sachs DH, Sykes M, Cosimi AB (2013) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 368:1850–1852
54. Owen RD (1945) Immunogenetic consequences of vascular anastomoses between bovine twins. Science 102:400–401
55. Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding RC, Sharma V, Fishman JA, Dey B, Ko DSC, Hertl M, Goes NB, Wong WC, Williams WW, Colvin RB, Sykes M, Sachs DH (2008) Brief report: HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 358:353–361
56. Buhler LH, Spitzer TR, Sykes M, Sachs DH, Delmonico FL, Tolkoff-Rubin N, Saidman SL, Sackstein R, McAfee S, Dey B, Colby C, Cosimi AB (2002) Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Transplantation 74:1405–1409
57. Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S (2008) Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 358:362–368
58. Andreola G, Chittenden M, Shaffer J, Cosimi AB, Kawai T, Cotter P, Locascio SA, Morokata T, Dey BR, Tolkoff-Rubin NT, Preffer F, Bonnefoix T, Kattleman K, Spitzer TR, Sachs DH, Sykes M (2011) Mechanisms of donor-specific tolerance in recipients of haploidentical combined bone marrow/kidney transplantation. Am J Transplant 11:1236–1247
59. Colson YL, Wren SM, Schuchert MJ, Patrene KD, Johnson PC, Boggs SS, Ildstad ST (1995) A nonlethal conditioning approach to achieve durable multilineage mixed chimerism and tolerance across major, minor, and hematopoietic histocompatibility barriers. J Immunol 155:4179–4188
60. Colson YL, Li H, Boggs SS, Patrene KD, Johnson PC, Ildstad ST (1996) Durable mixed allogeneic chimerism and tolerance by a nonlethal radiation-based cytoreductive approach. J Immunol 157:2820–2829
61. Sharabi Y, Sachs DH (1989) Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. J Exp Med 169:493–502
62. Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S (2012) Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant 12:1133–1145
63. Leventhal J, Miller J, Abecassis M, Tollerud DJ, Ildstad ST (2013) Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance. Clin Pharmacol Ther 93:36–45
64. Dahlke MH, Hoogduijn M, Eggenhofer E, Popp FC, Renner P, Slowik P, Rosenauer A, Piso P, Geissler EK, Lange C, Chabannes D, Mazzanti B, Bigenzahn S, Bertolino P, Kunter U, Introna M, Rambaldi A, Capelli C, Perico N, Casiraghi F, Noris M, Gotti E, Seifert M, Saccardi R, Verspaget HW, van Hoek B, Bartholomew A, Wekerle T, Volk HD, Remuzzi G, Deans R, Lazarus H, Schlitt HJ, Baan CC, Group MS (2009) Toward MSC in solid organ transplantation: 2008 position paper of the MISOT study group. Transplantation 88:614–619
65. Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ (2013) Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med 2:107–111
66. Perico N, Casiraghi F, Introna M, Gotti E, Todeschini M, Cavinato RA, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Marasa M, Golay J, Noris M, Remuzzi G (2011) Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility. Clin J Am Soc Nephrol 6:412–422
67. Opelz G, Dohler B (2008) Effect on kidney graft survival of reducing or discontinuing maintenance immunosuppression after the first year posttransplant. Transplantation 86:371–376
68. Heidt S, Wood KJ (2012) Biomarkers of operational tolerance in solid organ transplantation. Expert Opin Med Diagn 6:281–293
69. Sagoo P, Perucha E, Sawitzki B, Tomiuk S, Stephens DA, Miqueu P, Chapman S, Craciun L, Sergeant R, Brouard S, Rovis F, Jimenez E, Ballow A, Giral M, Rebollo-Mesa I, Le Moine A, Braudeau C, Hilton R, Gerstmayer B, Bourcier K, Sharif A, Krajewska M, Lord GM, Roberts I, Goldman M, Wood KJ, Newell K, Seyfert-Margolis V, Warrens AN, Janssen U, Volk HD, Soulillou JP, Hernandez-Fuentes MP, Lechler RI (2010) Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest 120:1848–1861
70. Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, Seyfert-Margolis VL, Immune Tolerance Network STSG (2010) Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest 120:1836–1847
71. Waki K, Sugawara Y, Mizuta K, Taniguchi M, Ozawa M, Hirata M, Nozawa M, Kaneko J, Takahashi K, Kadowaki T, Terasaki PI, Kokudo N (2013) Predicting operational tolerance in pediatric living-donor liver transplantation by absence of HLA antibodies. Transplantation 95:177–183
72. Chaudhuri A, Ozawa M, Everly MJ, Ettenger R, Dharnidharka V, Benfield M, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Li L, Sigdel TK, Hsieh SC, Dai H, Naesens M, Waskerwitz J, Salvatierra O Jr, Terasaki PI, Sarwal MM (2013) The clinical impact of humoral immunity in pediatric renal transplantation. J Am Soc Nephrol 24:655–664
73. +T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. Transplantation 81:398–407
74. Pallier A, Hillion S, Danger R, Giral M, Racape M, Degauque N, Dugast E, Ashton-Chess J, Pettre S, Lozano JJ, Bataille R, Devys A, Cesbron-Gautier A, Braudeau C, Larrose C, Soulillou JP, Brouard S (2010) Patients with drug-free long-term graft function display increased numbers of peripheral B cells with a memory and inhibitory phenotype. Kidney Int 78:503–513
75. Viklicky O, Krystufkova E, Brabcova I, Sekerkova A, Wohlfahrt P, Hribova P, Wohlfahrtova M, Sawitzki B, Slatinska J, Striz I, Volk HD, Reinke P (2013) B-cell-related biomarkers of tolerance are up-regulated in rejection-free kidney transplant recipients. Transplantation 95:148–154
76. Londono MC, Danger R, Giral M, Soulillou JP, Sanchez-Fueyo A, Brouard S (2012) A need for biomarkers of operational tolerance in liver and kidney transplantation. Am J Transplant 12:1370–1377
77. Ramakrishnan SK, Page A, Farris AB 3rd, Singh K, Leopardi F, Hamby K, Sen S, Polnett A, Deane T, Song M, Stempora L, Strobert E, Kirk AD, Larsen CP, Kean LS (2012) Evidence for kidney rejection after combined bone marrow and renal transplantation despite ongoing whole-blood chimerism in rhesus macaques. Am J Transplant 12:1755–1764
78. Xu H, Chilton PM, Huang Y, Schanie CL, Ildstad ST (2004) Production of donor T cells is critical for induction of donor-specific tolerance and maintenance of chimerism. J Immunol 172:1463–1471
79. Xu H, Chilton PM, Huang Y, Schanie CL, Yan J, Ildstad ST (2007) Addition of cyclophosphamide to T-cell depletion-based nonmyeloablative conditioning allows donor T-cell engraftment and clonal deletion of alloreactive host T-cells after bone marrow transplantation. Transplantation 83:954–963
80. Umemura A, Morita H, Li XC, Tahan S, Monaco AP, Maki T (2001) Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation. J Immunol 167:3043–3048
81. Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, King B, Elliott MJ, Herzig G, Herzig R, Ildstad ST (2012) Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med 4:124ra128
82. Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, Maloney DG, Storer B, Lange T, Chauncey T, Deininger M, Ponisch W, Anasetti C, Woolfrey A, Little MT, Blume KG, McSweeney PA, Storb RF (2003) Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 101:1620–1629
83. Jochum C, Beste M, Zellmer E, Graves SS, Storb R (2007) CD154 blockade and donor-specific transfusions in DLA-identical marrow transplantation in dogs conditioned with 1-Gy total body irradiation. Biol Blood Marrow Transplant 13:164–171
84. Ozyurek E, Cowan MJ, Koerper MA, Baxter-Lowe LA, Dvorak CC, Horn BN (2008) Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders. Bone Marrow Transplant 42:83–91
85. Foster BJ, Dahhou M, Zhang X, Platt RW, Hanley JA (2013) Relative Importance of HLA Mismatch and Donor Age to Graft Survival in Young Kidney Transplant Recipients. Transplantation 96:469–475
86. Plotnicki L, Kohl CD, Hocker B, Krupka K, Rahmel A, Pape L, Hoyer P, Marks SD, Webb NJ, Soylemezoglu O, Topaloglu R, Szabo AJ, Seeman T, Marlies Cornelissen EA, Knops N, Grenda R, Tonshoff B (2013) The CERTAIN Registry: A Novel, Web-Based Registry and Research Platform for Pediatric Renal Transplantation in Europe. Transplant Proc 45:1414–1417