transplantation tolerance


Summary: An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.

Top Publications

  1. Leishman A, Silk K, Fairchild P. Pharmacological manipulation of dendritic cells in the pursuit of transplantation tolerance. Curr Opin Organ Transplant. 2011;16:372-8 pubmed publisher
    ..immune suppression remains the intervention of choice for the treatment of allograft rejection, transplantation tolerance would achieve graft survival with fewer inherent risks...
  2. Kirk A, Turgeon N, Iwakoshi N. B cells and transplantation tolerance. Nat Rev Nephrol. 2010;6:584-93 pubmed publisher
    b>Transplantation tolerance is a state of immune unresponsiveness (or benign responsiveness) to the presence of specific, nonself antigens in the absence of chronic immunosuppressive therapy...
  3. Turka L, Wood K, Bluestone J. Bringing transplantation tolerance into the clinic: lessons from the ITN and RISET for the Establishment of Tolerance consortia. Curr Opin Organ Transplant. 2010;15:441-8 pubmed publisher
    Fundamental discoveries during the 1990s revolutionized our understanding of transplantation tolerance and our ability to create it in animal models...
  4. Garcia M, Ledgerwood L, Yang Y, Xu J, Lal G, Burrell B, et al. Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice. J Clin Invest. 2010;120:2486-96 pubmed publisher
    ..We propose that manipulating the common bone marrow monocyte progenitor could be a useful clinical therapeutic approach for inducing transplantation tolerance.
  5. Pilat N, Wekerle T. Transplantation tolerance through mixed chimerism. Nat Rev Nephrol. 2010;6:594-605 pubmed publisher
    ..This Review addresses recent advances in preclinical and clinical studies inducing transplantation tolerance through mixed chimerism and discusses both the potential and the challenges of this approach.
  6. Parsons R, Vivek K, Rostami S, Zekavat G, Ziaie S, Luo Y, et al. Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes. J Immunol. 2011;186:614-20 pubmed publisher
    A major obstacle to transplantation tolerance is humoral immunity...
  7. Issa F, Schiopu A, Wood K. Role of T cells in graft rejection and transplantation tolerance. Expert Rev Clin Immunol. 2010;6:155-69 pubmed
    ..This is followed by a detailed review of the current progress in the field of regulatory T-cell therapy in transplantation and the translation of this therapy to the clinical setting. ..
  8. Zhu Z, Fan L, Wang Q. Simultaneous blockade of costimulatory signals CD28-CD80 and CD40-CD154 combined with monoclonal antibody against CD25 induced a stable chimerism and tolerance without graft-versus-host disease in rat. Eur Surg Res. 2011;46:109-17 pubmed publisher
    ..Our aim was to explore a nontoxic strategy for the induction of mixed chimerism by pretreatment with anti-CD25 monoclonal antibody (mAb), cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4Ig) and anti-CD154 mAb...
  9. Batsford S, Dickenmann M, Dürmüller U, Hopfer H, Gudat F, Mihatsch M. Is monitoring of FOXP3 Treg cells in renal transplants during acute cellular rejection episodes useful?. Clin Nephrol. 2011;75:101-6 pubmed
    ..This phenomenon was not consistently seen in acute cellular rejection and the information does not appear to be of value for individual patient management in such cases. ..

More Information


  1. Chadha R, Heidt S, Jones N, Wood K. Th17: contributors to allograft rejection and a barrier to the induction of transplantation tolerance?. Transplantation. 2011;91:939-45 pubmed publisher
    ..Despite accumulating evidence, the precise impact of Th17 cells on transplant rejection and the induction of tolerance require further clarification. ..
  2. Kendal A, Chen Y, Regateiro F, Ma J, Adams E, Cobbold S, et al. Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance. J Exp Med. 2011;208:2043-53 pubmed publisher
    ..Empowering Foxp3(+) regulatory T cells in vivo offers a tractable route to avoid and correct tissue immunopathology. ..
  3. Casiraghi F, Perico N, Remuzzi G. Mesenchymal stromal cells to promote solid organ transplantation tolerance. Curr Opin Organ Transplant. 2013;18:51-8 pubmed publisher
    ..Further studies are needed to establish how and wherein these cells have to be administered and how they may function to safely modulate host immune response in vivo in clinical transplant setting. ..
  4. Gorantla V, Brandacher G, Schneeberger S, Zheng X, Donnenberg A, Losee J, et al. Favoring the risk-benefit balance for upper extremity transplantation--the Pittsburgh Protocol. Hand Clin. 2011;27:511-20, ix-x pubmed publisher
    ..Such therapies offer the promise of minimizing the risks, maximizing the benefits and optimizing outcomes of these innovative procedures. ..
  5. Newell K, Phippard D, Turka L. Regulatory cells and cell signatures in clinical transplantation tolerance. Curr Opin Immunol. 2011;23:655-9 pubmed publisher
    ..Rather than excluding or minimizing the contribution of regulatory cells to the development of transplantation tolerance, we suggest the possibility that multiple lineages of cells exert regulatory effects that contribute to ..
  6. Adams A, Newell K. B cells in clinical transplantation tolerance. Semin Immunol. 2012;24:92-5 pubmed publisher
    ..role for B cells in regulating or suppressing immune responses, a causative role for B cells in clinical transplantation tolerance has yet to be proven...
  7. Sachs D, Sykes M, Kawai T, Cosimi A. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011;23:165-73 pubmed publisher
    The induction of transplantation tolerance could liberate organ transplant recipients from the complications of life-long chronic immunosuppression...
  8. Boyman O, Krieg C, Letourneau S, Webster K, Surh C, Sprent J. Selectively expanding subsets of T cells in mice by injection of interleukin-2/antibody complexes: implications for transplantation tolerance. Transplant Proc. 2012;44:1032-4 pubmed publisher
    ..Preconditioning mice with these complexes leads to permanent acceptance of MHC-disparate pancreatic islets in the absence of immunosuppression. ..
  9. Parsons R, Redfield R, Rodriguez E, Mustafa M, Vivek K, Murayama M, et al. Primary B cell repertoire remodeling to achieve humoral transplantation tolerance. Semin Immunol. 2012;24:109-14 pubmed publisher
    ..Thus, achieving robust transplantation tolerance will require induction of tolerance in both the T- and B-cell compartments...
  10. Moraes Vieira P, Silva H, Takenaka M, Monteiro S, Lemos F, Saitovitch D, et al. Differential monocyte STAT6 activation and CD4(+)CD25(+)Foxp3(+) T cells in kidney operational tolerance transplanted individuals. Hum Immunol. 2010;71:442-50 pubmed publisher
    ..quot; The study of such patients may be important to understand the mechanisms involved in human transplantation tolerance. We compared the profile of CD4(+)CD25(+)Foxp3(+) T cells and the signaling pathways IL-6/STAT3 (signal ..
  11. LeGuern C, Akiyama Y, Germana S, Tanaka K, Fernandez L, Iwamoto Y, et al. Intracellular MHC class II controls regulatory tolerance to allogeneic transplants. J Immunol. 2010;184:2394-400 pubmed publisher
  12. Burns A, Chong A. Alloantibodies prevent the induction of transplantation tolerance by enhancing alloreactive T cell priming. J Immunol. 2011;186:214-21 pubmed publisher
    ..These observations highlight the ability of alloantibodies to function not only in classical humoral rejection but also as opsonins that facilitate the CD40-CD154-independent activation of alloreactive T cells. ..
  13. Dummer C, Carpio V, Gonçalves L, Manfro R, Veronese F. FOXP3+ regulatory T cells: from suppression of rejection to induction of renal allograft tolerance. Transpl Immunol. 2012;26:1-10 pubmed publisher
  14. Lombardi G, Sagoo P, Scotta C, Fazekasova H, Smyth L, Tsang J, et al. Cell therapy to promote transplantation tolerance: a winning strategy?. Immunotherapy. 2011;3:28-31 pubmed publisher
    ..Here, we have summarized our results both in the murine and human systems on the use of Treg-based strategies to induce tolerance to the transplanted organs. ..
  15. Regateiro F, Howie D, Cobbold S, Waldmann H. TGF-? in transplantation tolerance. Curr Opin Immunol. 2011;23:660-9 pubmed publisher
    TGF-? is a cytokine required for the induction and maintenance of transplantation tolerance in animal models. TGF-? mediates anti-inflammatory effects by acting on many immune cell-types...
  16. Akiyama Y, Caucheteux S, Vernochet C, Iwamoto Y, Tanaka K, Kanellopoulos Langevin C, et al. Transplantation tolerance to a single noninherited MHC class I maternal alloantigen studied in a TCR-transgenic mouse model. J Immunol. 2011;186:1442-9 pubmed publisher
  17. Fan H, Cao P, Game D, Dazzi F, Liu Z, Jiang S. Regulatory T cell therapy for the induction of clinical organ transplantation tolerance. Semin Immunol. 2011;23:453-61 pubmed publisher
    The pursuit of transplantation tolerance is the holygrail in clinical organ transplantation. It has been established that regulatory T cells (Tregs) can confer donor-specific tolerance in mouse models of transplantation...
  18. Safinia N, Leech J, Hernandez Fuentes M, Lechler R, Lombardi G. Promoting transplantation tolerance; adoptive regulatory T cell therapy. Clin Exp Immunol. 2013;172:158-68 pubmed publisher
    ..we will discuss how regulatory T cells (T(regs)) came to be recognized as an attractive way to promote transplantation tolerance. We will summarize the preclinical data, supporting the importance of these cells in the induction and ..
  19. PILLAI A, Hartford C, Wang C, Pei D, Yang J, Srinivasan A, et al. Favorable preliminary results using TLI/ATG-based immunomodulatory conditioning for matched unrelated donor allogeneic hematopoietic stem cell transplantation in pediatric severe aplastic anemia. Pediatr Transplant. 2011;15:628-34 pubmed publisher
    ..Although in limited patients, our results suggest that immunomodulatory TLI added to backbone CTX/ATG conditioning is a promising option for MUD HCT in SAA patients, which we will examine in a prospective clinical trial. ..
  20. Yamada Y, Boskovic S, Aoyama A, Murakami T, Putheti P, Smith R, et al. Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. Am J Transplant. 2012;12:330-40 pubmed publisher
    ..Using this modified approach, mixed chimerism was induced successfully in 11 of 13 recipients of previously placed renal allografts and long-term survival without immunosuppression could be achieved in at least 6 of these 11 animals. ..
  21. Hippen K, Riley J, June C, Blazar B. Clinical perspectives for regulatory T cells in transplantation tolerance. Semin Immunol. 2011;23:462-8 pubmed publisher
    ..This review will summarize the clinical trials conducted to date that have employed Tregs to prevent GVHD following HSCT and discuss recent advances in Treg cellular therapy. ..
  22. Gorantla V, Schneeberger S, Brandacher G, Sucher R, Zhang D, Lee W, et al. T regulatory cells and transplantation tolerance. Transplant Rev (Orlando). 2010;24:147-59 pubmed publisher
    ..The induction and maintenance of transplantation tolerance is the "Holy Grail" of transplantation...
  23. Siemionow M, Klimczak A. Immunodepletive anti-alpha/beta-TCR antibody in transplantation of composite tissue allografts: Cleveland Clinic research experience. Immunotherapy. 2009;1:585-98 pubmed publisher
  24. Newell K, Asare A, Kirk A, Gisler T, Bourcier K, Suthanthiran M, et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010;120:1836-47 pubmed publisher
    ..These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients. ..
  25. Leventhal J, Miller J, Abecassis M, Tollerud D, Ildstad S. Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance. Clin Pharmacol Ther. 2013;93:36-45 pubmed publisher
    ..This review presents a historic perspective of the quest for tolerance in organ transplantation, highlighting current clinical approaches...
  26. Francis R, Feng G, Tha In T, Lyons I, Wood K, Bushell A. Induction of transplantation tolerance converts potential effector T cells into graft-protective regulatory T cells. Eur J Immunol. 2011;41:726-38 pubmed publisher
  27. Pilat N, Hock K, Wekerle T. Mixed chimerism through donor bone marrow transplantation: a tolerogenic cell therapy for application in organ transplantation. Curr Opin Organ Transplant. 2012;17:63-70 pubmed publisher
    ..Both the potential for more widespread clinical application and the remaining hurdles and challenges of this tolerance approach will be discussed. ..
  28. Bozulic L, Wen Y, Xu H, Ildstad S. Evidence that FoxP3+ regulatory T cells may play a role in promoting long-term acceptance of composite tissue allotransplants. Transplantation. 2011;91:908-15 pubmed publisher
    ..In this study, we evaluated the role of Treg in peripheral tolerance to composite tissue allografts (CTA)...
  29. Goldstein D. Inflammation and transplantation tolerance. Semin Immunopathol. 2011;33:111-5 pubmed publisher
    ..Further investigation as to the innate inflammatory basis that controls the balance between immune acceptance and allograft rejection may lead us closer to the elusive goal of transplant tolerance acquisition. ..
  30. Tang Q, Bluestone J, Kang S. CD4(+)Foxp3(+) regulatory T cell therapy in transplantation. J Mol Cell Biol. 2012;4:11-21 pubmed publisher
  31. Redfield R, Rodriguez E, Parsons R, Vivek K, Mustafa M, Noorchashm H, et al. Essential role for B cells in transplantation tolerance. Curr Opin Immunol. 2011;23:685-91 pubmed publisher
    ..Therefore, the achievement of transplantation tolerance will likely require induction of both T and B cell tolerance to alloantigens...
  32. Velásquez Lopera M, Eaton V, Lerret N, Correa L, Decresce R, Garcia L, et al. Induction of transplantation tolerance by allogeneic donor-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells. Transpl Immunol. 2008;19:127-35 pubmed publisher
    ..have shown that recipient-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are involved in transplantation tolerance. However, it is not clear whether allogeneic donor-derived Tregs are able to regulate T cell ..
  33. Arslan E, Klimczak A, Siemionow M. Chimerism induction in vascularized bone marrow transplants augmented with bone marrow cells. Microsurgery. 2007;27:190-9 pubmed
    ..Transplantation of vascularized bone without chronic immunosuppression provides a substantial source of bone marrow cells, leading to the development of stable donor-specific chimerism. ..
  34. Morelli A, Thomson A. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol. 2007;7:610-21 pubmed
    ..In this Review, we integrate the available information on the role of DCs in the induction of tolerance, with a focus on transplantation. ..
  35. Casiraghi F, Azzollini N, Cassis P, Imberti B, Morigi M, Cugini D, et al. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. J Immunol. 2008;181:3933-46 pubmed
  36. Fehr T, Sykes M. Clinical experience with mixed chimerism to induce transplantation tolerance. Transpl Int. 2008;21:1118-35 pubmed publisher
    ..Directions for further research to make this approach applicable for a broader patient population are discussed. ..
  37. Xu Q, Lee J, Keller M, Burlingham W. Analysis of indirect pathway CD4+ T cells in a patient with metastable tolerance to a kidney allograft: possible relevance to superior graft survival of HLA class II closely matched renal allografts. Transpl Immunol. 2009;20:203-8 pubmed publisher
    ..This may favor the generation of a beneficial form of indirect pathway alloreactivity, i.e. allopeptide-specific CD4(+) T regulatory cells, in the context of long term DC microchimerism. ..
  38. Adeegbe D, Levy R, Malek T. Allogeneic T regulatory cell-mediated transplantation tolerance in adoptive therapy depends on dominant peripheral suppression and central tolerance. Blood. 2010;115:1932-40 pubmed publisher
    ..findings indicate that full tolerance induction is largely dependent on substantial Treg-mediated suppression and thymic deletion of alloreactive T cells and may represent general conditions for Treg-mediated transplantation tolerance.
  39. Li X, Rothstein D, Sayegh M. Costimulatory pathways in transplantation: challenges and new developments. Immunol Rev. 2009;229:271-93 pubmed publisher
  40. Waldmann H, Adams E, Fairchild P, Cobbold S. Regulation and privilege in transplantation tolerance. J Clin Immunol. 2008;28:716-25 pubmed publisher
    There are now many ways of achieving transplantation tolerance in rodents that do not require stem cell chimerism...
  41. Goldman M, Wood K. Translating transplantation tolerance in the clinic: where are we, where do we go?. Clin Exp Immunol. 2009;156:185-8 pubmed publisher
  42. Semiletova N, Shen X, Baibakov B, Andakyan A. Intensity of transplant chronic rejection correlates with level of graft-infiltrating regulatory cells. J Heart Lung Transplant. 2010;29:335-41 pubmed publisher
    ..Donor MHC Class I peptides can specifically prolong transplant survival and generate T-regs. The level of intragraft T-regs correlates with severity of TVS and IL-2/IL-4 down-regulation. ..
  43. Nasir S, Klimczak A, Sonmez E, Bozkurt M, Gibson S, Siemionow M. New composite tissue allograft model of vascularized bone marrow transplant: the iliac osteomyocutaneous flap. Transpl Int. 2010;23:90-100 pubmed publisher
    ..The IBOMC transplant proved to be a reliable composite tissue allotransplantation (CTA) model. Moreover, because of its robust bone marrow component and large skin component, it is applicable to studies on immunologic responses in CTA. ..
  44. Turka L, Lechler R. Towards the identification of biomarkers of transplantation tolerance. Nat Rev Immunol. 2009;9:521-6 pubmed publisher
    ..The development of biomarkers of transplantation tolerance holds promise to improve the care of organ allograft recipients, to provide surrogate end points of ..
  45. Warnecke G, Chapman S, Bushell A, Hernandez Fuentes M, Wood K. Dependency of the trans vivo delayed type hypersensitivity response on the action of regulatory T cells: implications for monitoring transplant tolerance. Transplantation. 2007;84:392-9 pubmed
    ..Here we tested the hypothesis that the assay can reveal control of allograft rejection by CD25CD4 regulatory T cells (Treg)...
  46. Moore D, Kim J, Sonawane S, Yeh H, Deng S, Lee K, et al. Progress toward antibody-induced transplantation tolerance. Crit Rev Immunol. 2007;27:167-218 pubmed
    b>Transplantation tolerance remains an elusive goal. Despite multiple animal models of tolerance induction using a variety of agents and protocols, it has yet to be achieved in humans with any predictability...
  47. Tanaka K, Albin M, Yuan X, Yamaura K, Habicht A, Murayama T, et al. PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection. J Immunol. 2007;179:5204-10 pubmed
    The PD-1:PDL pathway plays an important role in regulating alloimmune responses but its role in transplantation tolerance is unknown...
  48. Scandling J, Busque S, Dejbakhsh Jones S, Benike C, Millan M, Shizuru J, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008;358:362-8 pubmed publisher
    ..Adverse events requiring hospitalization were limited to a 2-day episode of fever with neutropenia. The patient has had neither rejection episodes nor clinical manifestations of graft-versus-host disease...
  49. Starzl T. Immunosuppressive therapy and tolerance of organ allografts. N Engl J Med. 2008;358:407-11 pubmed publisher
  50. Stapler D, Lee E, Selvaraj S, Evans A, Kean L, Speck S, et al. Expansion of effector memory TCR Vbeta4+ CD8+ T cells is associated with latent infection-mediated resistance to transplantation tolerance. J Immunol. 2008;180:3190-200 pubmed
    ..These results define the viral gene and immune cell types involved in latent infection-mediated resistance to allograft tolerance and underscore the influence of latent herpesviruses on allograft survival. ..
  51. Nakano T, Goto S, Lai C, Hsu L, Wong J, Kawamoto S, et al. Involvement of autoimmunity against nuclear histone H1 in liver transplantation tolerance. Transpl Immunol. 2008;19:87-92 pubmed publisher
    ..These results suggest that the sensitivity to nuclear antigens such as histone H1 may be a key factor determining the acceptance or rejection of donor liver grafts, at least in DA-PVG and DA-LEW combinations. ..
  52. Kawai T, Cosimi A, Spitzer T, Tolkoff Rubin N, Suthanthiran M, Saidman S, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;358:353-61 pubmed publisher
  53. Nakano T, Chen C, Goto S, Lai C, Hsu L, Kawamoto S, et al. The immunological role of lipid transfer/metabolic proteins in liver transplantation tolerance. Transpl Immunol. 2007;17:130-6 pubmed
    ..This study aimed to characterize the role of lipid transfer/metabolic proteins in liver transplantation tolerance. To identify the apo-E and adiponectin in post-OLT serum, Western analyses and enzyme-linked ..