The Pig as a Model to Assess the Effect of Class II MHC Antigen Matching on Renal Allograft Survival

  • M. D. Pescovitz
  • D. H. Sachs


Large animals such as dogs [1], monkeys [2], and swine [3] have been valuable models for transplantation biology both because of their size, which permits surgical manipulations similar to those in man, and because they provide an intermediate step between rodents and man in which to reexamine new experimental results. Although most biological principles are conserved among species, fine tuning of the immune system is in some cases different enough to make results in any one species not directly applicable to man. Among the known species differences which could potentially have clinical ramifications for transplants are differences in distribution of class II MHC antigens on vascular endothelium [4] and differences in levels of allogeneic resistance or graft-vs-host disease in the setting of bone marrow transplants [5, 6].


Major Histocompatibility Complex Mixed Lymphocyte Reaction Allograft Survival Minor Histocompatibility Antigen Miniature Swine 
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  1. 1.
    Bijnen AB, Westbroek DL, Obertop H, Vriesendorp HM (1979) Genetics of kidney allograft survival in dogs. I. Relevance of subregions of the major histocompatibility complex in recipients without immunosuppressive therapy. Transplantation 28:186–190PubMedCrossRefGoogle Scholar
  2. 2.
    van Es AA, Balner H (1978) Serologic matching for D locus antigens improves kidney allograft survival in rhesus monkeys. Transplantation 26:187–190PubMedCrossRefGoogle Scholar
  3. 3.
    Vaiman M, Gamier H, Kunklin A, Hay JM, Pare R, Bacour F, Fagniez PH, Villiers PA, Lecointre J, Bara MF, Nizza P (1972) The SL-A histocompatibility system in the Sus scrofa species. Transplantation 14:541–550PubMedCrossRefGoogle Scholar
  4. 4.
    Fabre JW (1982) Rat kidney allograft model: was it all too good to be true? Transplantation 34:223–225PubMedCrossRefGoogle Scholar
  5. 5.
    Almaraz R, Ballinger W, Sachs DH, Rosenberg SA (1983) The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic bone marrow transplantation. J Surg Res 34:133–144PubMedCrossRefGoogle Scholar
  6. 6.
    Filipovich AH, Ramsay NHC, McGlave P, Quinones R, Winslow C, Heinitz KJ, Arthur D, Kersey JH (1983) Mismatched bone marrow transplantation at the University of Minnesota: use of related donors other than HLA MLC identicle siblings and T cell depletion. In: Gale RP (ed) Recent advances in bone marrow transplantation. Liss, New York, NY, pp 769–783Google Scholar
  7. 7.
    Sachs DH, Leight G, Cone J, Schwarz S, Stuart L, Rosenberg S (1976) Transplantation in miniature swine. I. Fixation of the major histocompatibility complex. Transplantation 22:559–567PubMedCrossRefGoogle Scholar
  8. 8.
    Vaiman M, Renard C, LaFage P, Ameteau J, Nizza P (1970) Evidence for histocompatibility system in swine (SL-A). Transplantation 10:155–164PubMedCrossRefGoogle Scholar
  9. 9.
    Metzger J J, Lunney JK, Sachs DH, Rudikoff S (1982) Transplantation in miniature swine. XII. N-terminal sequences of class I histocompatibility antigens (SLA) and β 2 microglobulin. J Immunol 129:716–721PubMedGoogle Scholar
  10. 10.
    Singer DS, Camerini-Otero RD, Satz ML, Osborne B, Sachs D, Rudikoff S (1982) Characterization of a porcine genomic clone encoding a major histocompatibility antigen: expression in mouse L cells. Proc Natl Acad Sci USA 79:1403–1407PubMedCrossRefGoogle Scholar
  11. 11.
    Osborne BA, Lunney JK, Pennington L, Sachs DH, Rudikoff S (1983) Twodimensional gel analysis of swine histocompatibility antigens. J Immunol 131:2939–2944PubMedGoogle Scholar
  12. 12.
    Vaiman M, Chardon P, Renard P (1979) Genetic organization of the pig SLA complex. Studies on nine recombinants and biochemical and lysostrip analysis. Immunogenetics 9:353–361CrossRefGoogle Scholar
  13. 13.
    Lunney JK, Sachs DH (1978) Transplantation in miniature swine. IV. Chemical characterization of MSLA and la-like antigens. J Immunol 120:607–612PubMedGoogle Scholar
  14. 14.
    Lunney JK, Sachs DH (1979) Transplantation in miniature swine. V. Characterization of la antigens. J Immunol 122:623–627PubMedGoogle Scholar
  15. 15.
    Lunney JK, Osborne BA, Sharrow SO, Devaux C, Pierres M, Sachs DH (1983) Sharing of la antigens between species. IV. Interspecies cross-reactivity of monoclonal antibodies directed against polymorphic mouse la determinants. J Immunol 130:2786– 2793PubMedGoogle Scholar
  16. 16.
    Steinmetz M, Hood L (1983) Genes of the major histocompatibility complex in mouse and man. Science 222:727–733PubMedCrossRefGoogle Scholar
  17. 17.
    Steinmetz M (1985) Organization of MHC genes. In: Streilein JW, Ahmad F, Black S, Blomberg B, Voellmy RW (eds) Advances in gene technology: molecular biology of the immune system. Proceedings of the 17th Miami Winter Symposium. ICSU Press, Cambridge, England, pp 23–26Google Scholar
  18. 18.
    Pennington LR; Lunney JK, Sachs DH (1981) Transplantation in miniature swine. VIII. Recombination within the major histocompatibility complex of miniature swine. Transplantation 31:66–71PubMedCrossRefGoogle Scholar
  19. 19.
    Thistlethwaite JR Jr, Pennington LR, Lunney JK, Sachs DH (1983) Immunologic characterization of MHC recombinant swine: production of SLA class specific antisera and detection of la antigens on both B and non-B PBL. Transplantation 35:394–400PubMedCrossRefGoogle Scholar
  20. 20.
    Porter RR (1985) The complement genes of the HLA complex. In: Streilein JW, Ahmad F, Black S, Blomberg B, Voellmy RW (eds) Advances in gene technology: molecular biology of the immune system. Proceedings of the 17th Miami Winter Symposium. ICSU Press, Cambridge, England, pp 77–80Google Scholar
  21. 21.
    Chaplin DD, Woods DE, Whitehead AS, Goldberger G, Colten HR, Seidman JG (1983) Molecular map of the murine S region. Proc Natl Acad Sci USA 80:6947–6951PubMedCrossRefGoogle Scholar
  22. 22.
    Vaiman M, Hauptmann G, Mayer S (1978) Influence of the major histocompatibility complex in the pig (SLA) on serum haemolytic complement levels. J Immunogenet 5:59–65PubMedCrossRefGoogle Scholar
  23. 23.
    Rubinstein P, Vienne K (1982) Genetic control of the quantitative variation of erythrocytic glyoxalase-1 (GLO-1) in mice. Biochem Genet 20:153–162PubMedCrossRefGoogle Scholar
  24. 24.
    Stole V, Kunz HW, Gill III TS (1980) The linkage of glyoxylase-1 to the major histocompatibility complex in the rat. J Immunol 125:1167–1170Google Scholar
  25. 25.
    Weitkamp LR (1976) Linkage of GLO with HLA and BF. Effect of population and sex on recombination frequency. Tissue Antigens 7:273–279PubMedCrossRefGoogle Scholar
  26. 26.
    Shackelford DA, Kaufman JF, Korman AJ, Strominger JL (1982) HLA-DR antigens: Structure, separation of subpopulations, gene cloning and function. Immunol Rev 66:133–187PubMedCrossRefGoogle Scholar
  27. 27.
    Thistlethwaite JR Jr, Auchincloss H Jr, Pescovitz MD, Sachs DH (1984) Immunologic characterization of MHC recombinant swine: role of class I and II antigens in in vitro immune responses. J Immunogenet 11:9–19PubMedCrossRefGoogle Scholar
  28. 28.
    Norcross MA, Bentley DM, Margulies DH, Germain R (1984) Membrane la expression and antigen-presenting accessory cell function of L cells transfected with class II major histocompatibility complex genes. J Exp Med 160:1316–1337PubMedCrossRefGoogle Scholar
  29. 29.
    Vaiman M, Metzger JJ, Renard C, Vila JP (1978) Immune response gene(s) controlling the humoral anti-lysozyme response (Ir-lys) linked to the major histocompatibility complex SL-A in the pig. Immunogenetics 7:231–238PubMedCrossRefGoogle Scholar
  30. 30.
    Benson EM, Colvin RB, Russell PS (1985) Induction of la antigens in murine renal transplants. J Immunol 134:7–9PubMedGoogle Scholar
  31. 31.
    Hart DNJ, Fabre JW (1981) Major histocompatibility complex antigens in rat kidney, ureter, and bladder. Transplantation 31:318–325PubMedCrossRefGoogle Scholar
  32. 32.
    Lechler RI, Batchelor JR (1982) Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 155:31–41PubMedCrossRefGoogle Scholar
  33. 33.
    McKenzie JL, Beard ME J, Hart DNJ (1984) The effect of donor pretreatment on interstitial dendritic cell content and rat cardiac allograft survival. Transplantation 38:371–376PubMedCrossRefGoogle Scholar
  34. 34.
    Hart DNJ, Fuggle SV, Williams KA, Fabre JW, Ting A, Morris PJ (1981) Localization of HLA-ABC and DR antigens in human kidney. Transplantation 31:428–433PubMedCrossRefGoogle Scholar
  35. 35.
    Lafferty K (1980) Immunogenicity of foreign tissues. Transplantation 29:179–182PubMedCrossRefGoogle Scholar
  36. 36.
    Pescovitz MD, Sachs DH, Lunney JK, Hsu SM (1984) Localization of class II MHC antigens on porcine renal vascular endothelium. Transplantation 37:627–630PubMedCrossRefGoogle Scholar
  37. 37.
    Calne RY, Sells RA, Pena JR, Davis DR, Millard PR, Hebertson BM, Binns RM, Davies DAL (1969) Induction of immunological tolerance by porcine liver allografts. Nature 223:472–476PubMedCrossRefGoogle Scholar
  38. 38.
    Flye MW (1980) Immunological assessment of orthotopic liver transplantation in both outbred and MSLA defined inbred miniature swine. Thesis, Duke University, DurhamGoogle Scholar
  39. 39.
    Kirkman RL, Colvin RB, Flye MW, Leight GS, Rosenberg SA, Williams GM, Sachs DH (1979) Transplantation in miniature swine. VI. Factors influencing survival of renal allografts. Transplantation 28:18–23PubMedCrossRefGoogle Scholar
  40. 40.
    Leight GS, Kirkman R, Rasmusen BA, Rosenberg SA, Sachs DH, Terrill R, Williams GM (1978) Transplantation in miniature swine. III. Effect of MSLA and A-O blood group matching on skin allograft survival. Tissue Antigens 12:65–74PubMedCrossRefGoogle Scholar
  41. 41.
    Pennington LR, Flye MW, Kirkman RL, Thistlethwaite JR Jr, Williams GM, Sachs DH (1981) Transplantation in miniature swine. X. Evidence for non-SLA-linked immune response gene(s) controlling rejection of SLA-matched kidney allografts. Transplantation 32:315–320PubMedCrossRefGoogle Scholar
  42. 42.
    Schulak JA, Goeken NE, Nghiem DD, Corry RJ (1982) Effect of DR matching on rejection in first cadaver kidney transplantation. Transplantation 34:382–384PubMedCrossRefGoogle Scholar
  43. 43.
    Borleffs JCC, Marquet RL, deBy-Aghai Z, van Vreeswijk W, Neuhaus P, Balner H (1982) Kidney transplantation in rhesus monkeys: matching for D/DR antigens, pretransplant blood transfusions, and immunologic monitoring before transplantation. Transplantation 33:285–290PubMedCrossRefGoogle Scholar
  44. 44.
    Howard JC, Butcher GW (1981) The mechanism of graft rejection and the concept of antigenic strength. Scand J Immunol 14:687–691PubMedCrossRefGoogle Scholar
  45. 45.
    Hendricks GFJ, Claas FHJ, Persijn GG, Witvliet MD, Baldwin W, van Rood JJ (1983) HLA-DRw6-positive recipients are high responders in renal transplantation. Transplant Proc 14:1136–1138Google Scholar
  46. 46.
    Kirkman RL, Colvin RB, Flye MW, Williams GM, Sachs DH (1979) Transplantation in miniature swine. VII. Evidence for cellular immune mechanisms in hyperacute rejection of renal allografts. Transplantation 28:24–30PubMedCrossRefGoogle Scholar
  47. 47.
    Berg B, Moller E (1981) The influence of HLA-DR match on the outcome of cadaver renal transplantation in Stockholm during 1977–1980. Tissue Antigens 18:316–328PubMedCrossRefGoogle Scholar
  48. 48.
    Opelz G, Terasaki PI (1980) International histocompatibility workshop study on renal transplantation. In: Terasaki PI (ed) Histocompatibility testing 1980. UCLA Tissue Typing Laboratory, Los Angeles, pp 592–624Google Scholar
  49. 49.
    Aizawa M (1984) Transplantation immunobiology in the rat. In: Yamamura VY, Tada T (eds) Progress in immunology. Academic, Japan, pp 1439–1448Google Scholar
  50. 50.
    Paris A, Gunther E (1980) Kidney grafting between rats which carry recombinant major histocompatibility haplotypes. Immunogenetics 10:205–209CrossRefGoogle Scholar
  51. 51.
    Gallico GG, Butcher GW, Howard JC (1979) The role of subregions of the rat major histocompatibility complex in the rejection and passive enhancement of renal allografts. J Exp Med 149:244–253PubMedCrossRefGoogle Scholar
  52. 52.
    Borleffs JCC, de By-Aghai Z, Balner H (1981) Variable “predictive value” of matching for MLC nonresponsiveness in rhesus monkeys. Transplant Proc 13:1057–1060PubMedGoogle Scholar
  53. 53.
    Pescovitz MD, Thistlethwaite JR Jr, Auchincloss H Jr, Ildstad ST, Sharp TG, Terrill R, Sachs DH (1984) Effects of class II antigen matching on renal allograft survival in miniature swine. J Exp Med 160:1495–1505PubMedCrossRefGoogle Scholar
  54. 54.
    Pettirossi O, Sakai A, Kountz SL (1976) Differential survivals of Fl hybrid allografts in parental recipients. Transplantation 21:403–407PubMedCrossRefGoogle Scholar
  55. 55.
    Ting A, Morris PJ (1984) The influence of HLA-A,B and -DR matching and pregraft blood transfusions on graft and patient survival after renal transplantation in a single centre. Tissue Antigens 24:256–264PubMedCrossRefGoogle Scholar
  56. 56.
    Soulillou JP, Bignon JD, Houmant M, Ythier A, Cozian A, Faye R, Lecogic G, Guenel J (1982) Effect of HLA-A,B, and DR typing, pregraft blood transfusions, and positive anti-B lymphocyte cross matches on kidney-graft survival - a one-center prospective study. Transplant Proc 14:187–190Google Scholar
  57. 57.
    Watanabe K, Sada M, Uchida H, Endo T, Kashiwagi N (1983) Effects of DR matching and B–cell antibodies on related kidney graft survival. Transplant Proc 15:130–133Google Scholar
  58. 58.
    Isakov N, Bach FH (1984) High frequency of splenic anti-class I cytotoxic T lymphocyte precursors correlates with in vivo rejection of K/D region disparate thyroid and islet grafts in mice. J Immunol 132:50–56PubMedGoogle Scholar
  59. 59.
    Thorsby E, Ettenger R, Garovoy M (1984) Pretransplant immunologic considerations. Transplant Proc 16:1649–1653PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • M. D. Pescovitz
  • D. H. Sachs

There are no affiliations available

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