Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1987 Aug;61(4):421–428.

Immunosuppressive activity of serum from liver-grafted rats: in vitro specific inhibition of mixed lymphocyte reactivity by antibodies against class II RT1 alloantigens.

M Tsurufuji 1, K Ishiguro 1, T Shinomiya 1, T Uchida 1, N Kamada 1
PMCID: PMC1453439  PMID: 2450830

Abstract

The immunosuppressive activity of serum from PVG rats following orthotopic transplantation of DA liver has been examined in vitro. Liver grafts in this combination are never rejected, but induce a state of specific transplantation tolerance in the recipient. Serum from such tolerant animals was able to inhibit proliferation of normal PVG lymph node cells in response to DA stimulators in the mixed lymphocyte reaction (MLR); inhibition was specific for donor (DA) antigens. Interleukin-2 (IL-2) production during the MLR was also reduced. The production of anti-DA cytotoxic T cells developing in the MLR was not affected, but the total yield of such cells was reduced. Evidence was obtained that part of the inhibitory serum activity was due to IgG antibody against class II RT1a alloantigens. Thus, a purified IgG fraction retained much of the inhibitory activity which could be removed by an anti-IgG absorbent. Studies of MLR inhibition in different rat strains indicated the anti-class II specificity of the inhibitory IgG. Lymph node cells from DA-liver-grafted PVG rats responded normally against DA stimulators in vitro, and this MLR was also blocked by the inhibitory IgG. Our results suggest that anti-class II allo-antibody may play a role in immunosuppression and long-term graft survival following liver transplantation in this combination.

Full text

PDF
421

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bos E. S., van der Doelen A. A., van Rooy N., Schuurs A. H. 3,3',5,5' - Tetramethylbenzidine as an Ames test negative chromogen for horse-radish peroxidase in enzyme-immunoassay. J Immunoassay. 1981;2(3-4):187–204. doi: 10.1080/15321818108056977. [DOI] [PubMed] [Google Scholar]
  2. Butcher G. W., Corvalán J. R., Licence D. R., Howard J. C. Immune response genes controlling responsiveness to major transplantation antigens. Specific major histocompatibility complex-linked defect for antibody responses to class I alloantigens. J Exp Med. 1982 Jan 1;155(1):303–320. doi: 10.1084/jem.155.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butcher G. W., Howard J. C. A recombinant in the major histocompatibility complex of the rat. Nature. 1977 Mar 24;266(5600):362–364. doi: 10.1038/266362a0. [DOI] [PubMed] [Google Scholar]
  4. Engemann R., Ulrichs K., Thiede A., Müller-Ruchholtz W., Hamelmann H. Value of a physiological liver transplant model in rats. Induction of specific graft tolerance in a fully allogeneic strain combination. Transplantation. 1982 May;33(5):566–568. [PubMed] [Google Scholar]
  5. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971 Sep;8(9):871–874. doi: 10.1016/0019-2791(71)90454-x. [DOI] [PubMed] [Google Scholar]
  6. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  7. Houssin D., Gigou M., Franco D., Bismuth H., Charpentier B., Lang P., Martin E. Specific transplantation tolerance induced by spontaneously tolerated liver allograft in inbred strains of rats. Transplantation. 1980 May;29(5):418–419. doi: 10.1097/00007890-198005000-00015. [DOI] [PubMed] [Google Scholar]
  8. Howard J. C., Butcher G. W., Licence D. R., Galfrè G., Wright B., Milstein C. Isolation of six monoclonal alloantibodies against rat histocompatibility antigens: clonal competition. Immunology. 1980 Sep;41(1):131–141. [PMC free article] [PubMed] [Google Scholar]
  9. Howard J. C., Butcher G. W. The mechanism of graft rejection and the concept of antigenic strength. Scand J Immunol. 1981 Dec;14(6):687–691. doi: 10.1111/j.1365-3083.1981.tb00611.x. [DOI] [PubMed] [Google Scholar]
  10. Kamada N., Brons G., Davies H. S. Fully allogeneic liver grafting in rats induces a state of systemic nonreactivity to donor transplantation antigens. Transplantation. 1980 May;29(5):429–431. doi: 10.1097/00007890-198005000-00021. [DOI] [PubMed] [Google Scholar]
  11. Kamada N., Davies H. S., Roser B. J. Fully allogeneic liver grafting and the induction of donor-specific unreactivity. Transplant Proc. 1981 Mar;13(1 Pt 2):837–841. [PubMed] [Google Scholar]
  12. Kamada N., Davies H. S., Roser B. Reversal of transplantation immunity by liver grafting. Nature. 1981 Aug 27;292(5826):840–842. doi: 10.1038/292840a0. [DOI] [PubMed] [Google Scholar]
  13. Kamada N., Davies H. S., Wight D., Culank L., Roser B. Liver transplantation in the rat. Biochemical and histological evidence of complete tolerance induction in non-rejector strains. Transplantation. 1983 Apr;35(4):304–311. [PubMed] [Google Scholar]
  14. Kamada N., Shinomiya T., Tamaki T., Ishiguro K. Immunosuppressive activity of serum from liver-grafted rats. Passive enhancement of fully allogeneic heart grafts and induction of systemic tolerance. Transplantation. 1986 Dec;42(6):581–587. doi: 10.1097/00007890-198612000-00002. [DOI] [PubMed] [Google Scholar]
  15. Kamada N. The immunology of experimental liver transplantation in the rat. Immunology. 1985 Jul;55(3):369–389. [PMC free article] [PubMed] [Google Scholar]
  16. Kamada N., Wight D. G. Antigen-specific immunosuppression induced by liver transplantation in the rat. Transplantation. 1984 Sep;38(3):217–221. doi: 10.1097/00007890-198409000-00004. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Limmer J., Herbertson B. M., Calne R. Y. Orthotopic rat liver transplantation using different combinations of four inbred strains. Eur Surg Res. 1980;12(5):343–348. doi: 10.1159/000128140. [DOI] [PubMed] [Google Scholar]
  19. Schwartz R. H., Fathman C. G., Sachs D. H. Inhibition of stimulation in murine mixed lymphocyte cultures with an alloantiserum directed against a shared Ia determinant. J Immunol. 1976 Apr;116(4):929–935. [PubMed] [Google Scholar]
  20. Zimmermann F. A., Butcher G. W., Davies H. S., Brons G., Kamada N., Türel O. Techniques for orthotopic liver transplantation in the rat and some studies of the immunologic responses to fully allogeneic liver grafts. Transplant Proc. 1979 Mar;11(1):571–577. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES