Skip to main content
SpringerLink
Log in

Genetic control of rat heart allograft rejection: effect of different MHC and non-MHC incompatibilities

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

We investigated the genetic control of heterotopic heart allograft rejection using a family of standard inbred, major histocompatibility complex (MHC)-congenic, and intra-MHC recombinant rat strains. Gene products of the various regions within the rat MHC differed markedly in their capacity to induce rejection. Isolated incompatibility at class I antigens encoded by theRT1. A andRT1. C regions failed to induce rejection within the observation period of 100 days, whereas class II antigens encoded by theRT1.B/D region provoked rapid rejection within 10 days. By comparison of the rejection times of isolated and combined incompatibilities a number of functional interactions could be demonstrated between individual MHC regions which either prolonged or shortened allograft survival. In contrast to rapid rejection of MHC-mismatched heart allografts, differences at non-MHC histocompatibility antigens were associated with graft survival beyond 100 days, although chronic rejection of variable severity was detected histologically. Disparity at non-MHC plus class I antigens, however, provoked acute heart allograft rejection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Billingham, R. E., Hodge, B. A., and Silvers, W. K.: An estimate of the number of histocompatibility loci in the rat.Proc Natl Acad Sci USA 48: 138–147, 1962

    CAS  PubMed  Google Scholar 

  • Butcher, G. W. and Howard, J. C.: Genetic control of transplant rejection.Transplantation 34: 161–166, 1982

    CAS  PubMed  Google Scholar 

  • Butcher, G. W. and Howard, J. C.: The MHC of the laboratory rat, Rattus norvegicus.In D. M. Weir (ed.):Handbook of Experimental Immunology, Vol. 3, pp. 101.1–101.18, Blackwell, Oxford, 1986

    Google Scholar 

  • Burdick, J. F. and Clow, L. W.: Rejection of murine cardiac allografts. I. Relative roles of major and minor antigens.Transplantation 42: 67–72, 1986

    CAS  PubMed  Google Scholar 

  • Corry, R. J., Win, H. J., and Russell, P. S.: Primarily vascularized allografts in mice. The role of H-2D, H-2K and non-H-2 antigens in rejection.Transplantation 16: 343–350, 1973

    CAS  PubMed  Google Scholar 

  • Faustman, D., Hauptfeld, V., Lacy, P., and Davie, J.: Prolongation of murine islet allograft survival by pretreatment of islets with antibody directed to Ia determinants.Proc Natl Acad Sci USA 78: 5156–5159, 1981

    CAS  PubMed  Google Scholar 

  • Gill, T. J. III, Kunz, H. W., Misra, D. N., and Cortese Hassett, A. L.: The major histocompatibility complex of the rat.Tranplantation 43: 773–785, 1987

    Article  CAS  Google Scholar 

  • Günther, E.: Immunogenetic aspects of organ transplantation in the rat.In A. Thiede, E. Deltz, R. Engemann, H. Hamelmann (eds.):Microsurgical Models in Rats for Transplantation Research, pp. 83–94, Springer-Verlag, Berlin, Heidelberg, 1985

    Google Scholar 

  • Günther, E. and Wurst, W.: Cytotoxic T lymphocytes of the rat are predominantly restricted by RT1.A and non RT1.C-determined major histocompatibility class I antigens.Immunogenetics 20: 1–12, 1984

    Article  PubMed  Google Scholar 

  • Günther, E., Wurst, W., Wonigeit, K., and Epplen, J. T.: Analysis of the rat major histocompatibility system by Southern blot hybridization.J Immunol 134: 1257–1261, 1985

    PubMed  Google Scholar 

  • Guttmann, R. D., Forbes, R. D. C., Fuks, A., and Hibberd, J.: Rejection and prolongation of rat cardiac allografts across intramajor histocompatibility complex (MHC) and non-MHC differences using congenic lines: evidence for decreased class I immunogenicity.Transplant Proc 17: 1911–1913, 1985

    Google Scholar 

  • Hart, D. N. J. and Fabre, J. W.: Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, nut not brain.J Exp Med 154: 347–361, 1981

    Article  CAS  PubMed  Google Scholar 

  • Katz, S. M., Liebert, M., Gill, T. J. III, Kunz, H. W., Cramer, D. V., and Guttmann, R. D.: The relative roles of MHC and non-MHC genes in heart and skin allograft survival.Transplantation 36: 96–101, 1983

    CAS  PubMed  Google Scholar 

  • Klein, J., Chiang, C. L., Lofgreen, J., and Steinmuller, D.: Participation of H-2 regions in heart-transplant rejection.Transplantation 22: 384–390, 1976

    CAS  PubMed  Google Scholar 

  • Klempnauer, J., Wonigeit, K., Steiniger, B., Günther, E., and Pichlmayr, R.: Pancreas whole organ transplantation in the rat. Differential effect of individual MHC regions.Transplant Proc 15: 1308–1310, 1983a

    Google Scholar 

  • Klempnauer, J., Wonigeit, K., Günther, E., and Pichlmayr, R.: Pancreas whole organ transplantation in the rat: evidence for strong effect of non-MHC incompatibilities.Transplant Proc 15: 1649–1651, 1983b

    Google Scholar 

  • Klempnauer, J., Wonigeit, K., and Steiniger, B.: Transplantation effects of the RT1.C region in rat heart and pancreas grafting.Transplant Proc 17: 1893–1896, 1985

    Google Scholar 

  • Kohoutová, M., Günther, E., and Štark, O.: Genetic definition of a further gene region and identification of at least three different histocompatibility genes in the rat major histocompatibility system.Immunogenetics 11: 483–490, 1980

    Article  Google Scholar 

  • Lechler, R. I. and Batchelor, J. R.: Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells.J Exp Med 155: 31–41, 1982

    Article  CAS  PubMed  Google Scholar 

  • Lobel, S. A. and Cramer, D. V.: Demonstration of a new genetic locus in the major histocompatibility system of the rat.Immunogenetics 13: 465–673, 1981

    Article  CAS  PubMed  Google Scholar 

  • Lowry, R. P. and Blackburn, J. K.: Studies on rejection of heart grafts bearing isolated RT1A-encoded class I disparities.Transplant Proc 16: 1118–1123, 1984

    CAS  PubMed  Google Scholar 

  • Mann, H. B. and Whitney, D. R.: On a test of whether one of two random variables is stochastically larger than the other.Ann Math Statist 18: 50–60, 1947

    Google Scholar 

  • Milton, A. D. and Fabre, J. W.: Massive induction of donor type class I and class II MHC antigens in rejecting cardiac allografts in the rat.J Exp Med 161: 98–112, 1985

    Article  CAS  PubMed  Google Scholar 

  • Ono, K. and Lindsay, E. S.: Improved technique of heart transplantation in rats.J Thorac Cardiovasc Surg 57: 225, 1969

    CAS  PubMed  Google Scholar 

  • Paris, A. and Günther, E.: Kidney grafting between rats which carry recombinant major histocompatibility haplotypes.Immunogenetics 10: 205–209, 1980

    Article  Google Scholar 

  • Peugh, W. N., Superina, R.-A., Wood, K. J., and Morris, P. J.: The role ofH-2 and non-H-2 antigens and genes in the rejection of murine cardiac allografts.Immunogenetics 23: 30–37, 1986

    Article  CAS  PubMed  Google Scholar 

  • Rozing, J., Bonthuis, F., Joling, P., Vaessen, L. M. B., and Lameijer, L. D. F.: The influence of RT1 subregion differences on cardiac allograft survival.Transplant Proc 15: 1647–1648, 1983

    Google Scholar 

  • Soulillou, J. P., Blandin, F., Günther, E., and Lemoine, V.: Genetics of the blood transfusion effect on heart allografts in rats.Transplantaton 38: 63–67, 1984

    CAS  Google Scholar 

  • Steiniger, B. and Klempnauer, J.: Distinct histological patterns of acute, prolonged and chronic rejection in vascularized rat pancreas allografts.Am J Pathol 124: 253–252, 1986a

    CAS  PubMed  Google Scholar 

  • Steiniger, B. and Klempnauer, J.: Donor type MHC positive cells in the host spleen after rat organ transplantation. Differences between pancreas and heart allograft recipients.Transplantation 41: 787–789, 1986b

    CAS  PubMed  Google Scholar 

  • Steiniger, B. and Klempnauer, J., and Wonigeit, K.: Phenotype and histological distribution of interstitial dendritic cells in the rat pancreas, liver, heart and kidney.Transplantation 38: 169–175, 1985a

    Google Scholar 

  • Steiniger, B. and Klempnauer, J., and Wonigeit, K.: Expression of class I and class II major histocompatibility complex antigens during heart allograft rejection in the rat.Transplant Proc 17: 1907–1910, 1985b

    Google Scholar 

  • Stepkowski, S. M., Raza-Ahmad, A., and Duncan, W. R.: The role of class I and class II MHC antigens in the rejection of vascularized heart allografts in the mice.Transplantation 44: 753–759, 1987

    CAS  PubMed  Google Scholar 

  • Stewart, R., Butcher, G., Herbert, J., and Roser, B.: Graft rejection in a congenic panel of rats with defined immune response genes for MHC class I antigen.Transplantation 40: 427–432, 1985

    CAS  PubMed  Google Scholar 

  • Stock, W. and Günther, E.: Serologic and cellular characterization of products of a new major histocompatibility gene region, RT1.C, of the rat: possible homology to mouse H-2 Qa.J Immunol 128: 1923–1928, 1982

    CAS  PubMed  Google Scholar 

  • Tsuchimoto, S., Mizuno, K., Matsuno, Y., Niiyama, T., Cramer, D., Natori, T., and Aizawa, M.: The effect of RT1 subregion differences on liver allograft survival in the rat.Transplant Proc 17: 1900–1901, 1985

    Google Scholar 

  • Watters, J. W. F., Locker, J. D., Kunz, H. W., and Gill, T. J. III: Polymorphism and mapping of the class II genes in the rat:RT1.B, RT1.D, andRT1.H, a newDP-like region.Immunogenetics 26: 220–229, 1987

    Article  CAS  PubMed  Google Scholar 

  • White, E., Hildemann, W. H., and Mullen, Y.: Chronic kidney allograft reactions in rats.Transplantation 8: 602–617, 1969

    Article  CAS  PubMed  Google Scholar 

  • Wonigeit, K., Hedrich, H. J., and Günther, E.: Serologic and histogenic analysis of apparently identical RT1 haplotypes.Transplant Proc 11: 1584–1587, 1979

    CAS  PubMed  Google Scholar 

  • Wurst, W., Rothermel, E., and Günther, E.: Genetic mapping ofC4 andBf complement genes in the rat major histocompatibility complex.Immunogenetics 28: 57–60, 1988

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule, Konstanty-Gutschow-Str. 8, D-3000, Hannover 61, Federal Republic of Germany

    J. Klempnauer & R. Lück

  2. Abteilung V, Zentrum Anatomie, Medizinische Hochschule, D-3000, Hannover 61, Federal Republic of Germany

    B. Steiniger

  3. Abteilung Immungenetik, Zentrum Hygiene und Humangenetik der Universität, D-3400, Göttingen, Federal Republic of Germany

    E. Günther

Authors
  1. J. Klempnauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Steiniger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Lück
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Günther
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klempnauer, J., Steiniger, B., Lück, R. et al. Genetic control of rat heart allograft rejection: effect of different MHC and non-MHC incompatibilities. Immunogenetics 30, 81–88 (1989). https://doi.org/10.1007/BF02421535

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02421535

Keywords

Search

Navigation