Immunobiology of Allograft Destruction

  • M. H. Sayegh
  • D. R. Salomon


The past decade has been marked by a veritable explosion in our understanding of the immune response to alloantigens and the mechanisms of graft rejection. We can now consider both cellular and molecular events that directly impact on the function and survival of transplanted organs. The immune response that once may have seemed a relatively simple set of cell-cell interactions has now been expanded into such marvelous detail that the resulting complexity is a major and daunting challenge for both clinicians and scientists.


Major Histocompatibility Complex Major Histocompatibility Complex Class Acute Rejection Chronic Rejection Major Histocompatibility Complex Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Krensky AM, Weiss A, Crabtree G, Davis MM, Parham P, T-lymphocyte-antigen interactions in transplant rejection. N Engl J Med. 1990;322:510.PubMedCrossRefGoogle Scholar
  2. 2.
    Bjorkman PJ, Saper MA, Sumraoui B, Bennett WS, Strominger JL, Wiley DC. The foreign antigen binding site and T cell recognition regions of class I histocompatibilily antigen. Nature. 1987;329:512.PubMedCrossRefGoogle Scholar
  3. 3.
    Rotzschke O, Falk K. Naturally-occurring peptides antigens derived from the MHC class-I-restricted processing pathway. Immunol Today. 1991; 12:447.PubMedCrossRefGoogle Scholar
  4. 4.
    Spies T, Bresnahan M, Bahram S et al. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature, 1990;348:744.PubMedCrossRefGoogle Scholar
  5. 5.
    Brown JH, Jardetzky TS, Gorga JC et al. Three-dimensional structure of the human class II hislocompatibility antigen HLA-DRI. Nature, 1993;364:33.PubMedCrossRefGoogle Scholar
  6. 6.
    Chicz RM, Urban RG, Lane WS et al. Predominant naturally processed peptides bound to HLA-DR1 are derived trom MHC-related molecules and are heterogeneous in size. Nature. 1992;358:764.PubMedCrossRefGoogle Scholar
  7. 7.
    Chicz RM, Urban RG, Gorga JC, Vignali AA, Lane WS, Srominger JL. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med. 1993; 178:27.PubMedCrossRefGoogle Scholar
  8. 8.
    Shoskes DA, Wood KJ. Indirect presentation of MHC antigens in transplantation. Immunol Today. 1994;15:32.PubMedCrossRefGoogle Scholar
  9. 9.
    Sayegh MH, Watschinger B, Carpenter CB. Mechanisms of T cell recognition of alloantigen; the role of peptides. Transplantation. 1994;57:1295.PubMedCrossRefGoogle Scholar
  10. 10.
    Lehler RI, Batchelor JR. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 1982; 155:31.CrossRefGoogle Scholar
  11. 11.
    Lechler RI, Batchelor JR. Immunogenicity of retransplanted rat kidney allografts; effects of including chimerism in the first recipient and quantitative studies on immunosuppression of the second recipient. J Exp Med. 1982;156:1835.PubMedCrossRefGoogle Scholar
  12. 12.
    Sherman AL, Chattopadhyay S. The molecular basis of allorecognition. Annu Rev Immunol. 1993;11:385.PubMedCrossRefGoogle Scholar
  13. 13.
    Kappler JW, Roehin N, Marrack PC. T cell tolerance by clonal elimination in the thymus. Cell. 1987;49:273.PubMedCrossRefGoogle Scholar
  14. 14.
    Sprent J, Lo D, Gao KK, Ron Y. T cell selection in the thymus. Immunol Rev. 1988;101:173.PubMedCrossRefGoogle Scholar
  15. 15.
    Nickerson PW, Steurer W, Steiger J, Strom TB. In pursuit of the ‘Holy Grail’: allograft tolerance. Kidney Int. 1994;45:S40.Google Scholar
  16. 16.
    Charlton B, Auchincloss HJ, Fathman CG. Mechanisms of transplantation tolerance. Annu Rev Immunol. 1994;12:207.CrossRefGoogle Scholar
  17. 17.
    Starzl TE, Demetris AJ, Murase N, Thomson AW, Trucoo M, Ricordi C. Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation. Immunol Today. 1993;14:326.PubMedCrossRefGoogle Scholar
  18. 18.
    Thomas TM, Carver FM, Cunningham RC, Olson LC, Thomas FT. Kidney allograft tolerance in primates without chronic immunosuppression — the role of veto cells. Transplantation. 1991;51:198.PubMedCrossRefGoogle Scholar
  19. 19.
    Thomas JM, Carver FM, Kasten-Jolly J et al. Further studies of veto activity in rhesus monkey bone marrow relative to allograft tolerance and chimerism. Transplantation 1994;57:101.PubMedCrossRefGoogle Scholar
  20. 20.
    Qin S, Cobbold SP, Pope H et al. ‘Infectious’ transplantation tolerance. Science. 1993;259:974.PubMedCrossRefGoogle Scholar
  21. 21.
    Khoury SJ, Hancock WW, Weiner HL. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor-β and prostaglandin E expression in the brain. J Exp Med. 1992;176:1355.PubMedCrossRefGoogle Scholar
  22. 22.
    Lowry RP, Takeuchi T. Immunologic tolerance and its relationship to clinical transplantation. In: Burdick J, Racusen L, Solez K, Williams M, editors. Kidney transplant rejection, 2nd edn. New York Dekker: 1992;83–233.Google Scholar
  23. 23.
    Nickerson P, Steurer W, Steiger J, Zheng X, Steele AW, Strom TB. Cytokines and the Th1/Th2 paradigm in transplantation. Curr Opin Immunol. 1994;6:757.PubMedCrossRefGoogle Scholar
  24. 24.
    Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348.PubMedGoogle Scholar
  25. 25.
    Sayegh MH, Akalin E, Hancock WW, Russell ME, Carpenter CB, Turka IA. CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med. 1995;181:1869.PubMedCrossRefGoogle Scholar
  26. 26.
    Strober S, Million M, Schubert M el al. Acquired immune tolerance to cadaver renal allografts. A study of three patients with total lymphoid irradiation. N Engl J Med. 1989;321:28.PubMedCrossRefGoogle Scholar
  27. 27.
    Sayegh MH, Fine NA, Smith JL, Rennke HG, Milford EL, Tilney NL. Immunologic tolerance to renal allografts after bone marrow transplantation from the same donors. Ann Intern Med. 1991;114:954.PubMedGoogle Scholar
  28. 28.
    Billingham RE, Brent L, Medawar P. Actively acquired tolerance to foreign cells. Nature. 1953; 172:603.PubMedCrossRefGoogle Scholar
  29. 29.
    Posselt AM, Barker CF, Tomaszewski JE, Markmann JF, Choti MA, Naji A. Induction of donor-specific unresponsiveness by intrathymic islet transplantation. Science. 1990;249:1293.PubMedCrossRefGoogle Scholar
  30. 30.
    Remuzzi G, Perico N, Carpenter CB, Sayegh MH. The thymic way to transplantation tolerance. J Am Soc Nephrol 1995;5:1639.PubMedGoogle Scholar
  31. 31.
    Madsen JC, Superina RA, Wood KJ, Morris PJ. Immunological unresponsiveness induced by recipient cells transfected with donor MHC genes. Nature. 1988;332:161.PubMedCrossRefGoogle Scholar
  32. 32.
    Fraser CC, Sykes M, Lee RS, Sachs DH, Le Guern C. Specific unresponsiveness to a retroviral-transfected class I antigen is controlled by the helper pathway. J Immunol. 1995;154:1587.PubMedGoogle Scholar
  33. 33.
    Lagaaij EM, Hennemann IPH, Ruigrok M et al. Effect of one HLA-DR antigen matched and completely HLA-DR mismatched blood transfusions on survival of heart and kidney allografts. N Engl J Med. 1989;321:705.CrossRefGoogle Scholar
  34. 34.
    van Twuyver E, Mooijaart RJ, ten Berge IJ et al. Pretransplantation blood transfusions revisited. N Engl J Med. 1991;325:1210.PubMedCrossRefGoogle Scholar
  35. 35.
    Barber WH, Mankin JA, Laskow DA et al. Long-term results of a controlled prospective study with transfusion of donor-specific bone marrow in 57 cadaver renal allograft recipients. Transplantation. 1991;51:70.PubMedCrossRefGoogle Scholar
  36. 36.
    Krensky AM, Clayberger C. The induction of tolerance to alloantigens using HLA based synthetic peptides. Curr Opin Immunol. 1994;6:791.PubMedCrossRefGoogle Scholar
  37. 37.
    Sayegh MH, Krensky AM. Novel immunotherapeutic strategies using MHC derived peptides. Kidney Int. 1995 (In press).Google Scholar
  38. 38.
    Nisco S, Vriens P, Hoyt G et al. Induction of allograft tolerance in rats by an HLA class I derived peptide and cyclosporin A. J Immunol. 1994;152:3786.PubMedGoogle Scholar
  39. 39.
    Murphy B, Akalin E, Watschinger B, Carpenter CB, Sayegh MH. Inhibition of the alloimmune response with synthetic non-polymorphic class II MHC peptides. Transplant Proc. 1995;27:409.PubMedGoogle Scholar
  40. 40.
    June CH, Bluestone JA, Nadler LM, Thompson CB. The B7 and CD28 receptor families. Immunology Today 1994;15:321.PubMedCrossRefGoogle Scholar
  41. 41.
    Bluestone JA. New perspectives of CD28-B7-mediateti T cell costimulation. Immunity. 1995;2:555.PubMedCrossRefGoogle Scholar
  42. 42.
    Thompson CB. Distinct roles for the costimulatory ligands B7-1 and B7-2 in T helper cell differentiation. Cell. 1995;81:979.PubMedCrossRefGoogle Scholar
  43. 43.
    Sayegh MH, Turka LA. T cell costimulatory pathways: promising novel targets for immunosuppression and tolerance induction. J Am Soc Nephrol. 1995 (In press).Google Scholar
  44. 44.
    Linsley PS, Lcdbctter JA. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191.PubMedGoogle Scholar
  45. 45.
    Krensky AM, Buelow R, Clayberger C. HLA class I-derived peptides as novel immunosuppressive agents. In: Salomon DR, editor. Adhesion molecules, fusion proteins, novel peptides and monoclonal antibodies. (Glenview: Physicians and Scientists Publ. Co.). 1995;1–12.Google Scholar
  46. 46.
    Sayegh MH, Carpenter CB. Novel strategies in transplantation: Synthetic MHC class II peptides. In: Salomon DR, editor. Adhesion molecules, fusion proteins, novel peptides, and monoclonal antibodies. (Glenview: Physicians and Scientists Publ. Co.). 1995;13–26.Google Scholar
  47. 47.
    Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science. 1995;268:233.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • M. H. Sayegh
  • D. R. Salomon

There are no affiliations available

Personalised recommendations