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. 1984 Jul;57(1):85–92.

Study of cellular immunity in experimental autoimmune hepatitis in mice.

Y Mori, T Mori, H Yoshida, S Ueda, K Iesato, Y Wakashin, M Wakashin, K Okuda
PMCID: PMC1536088  PMID: 6430615

Abstract

This study was undertaken to produce experimental autoimmune hepatitis in mice, and to examine the role of liver specific lipoprotein (LSP), if any, and of cellular immunity in such a model. After immunization of three strains of mice (C57BL/6, C3H/He and BALB/c) with syngeneic crude liver proteins, most prominent liver changes histologically mimicking human hepatitis were produced in the liver of C57BL/6 (B6) mice. Antigenic and immunogenic activity of LSP in the crude liver proteins was decreased by the treatment of freezing and thawing, and the recovery of the antigenic activity seemed to correlate with the susceptibility of immunized mice to the induction of liver damage. Autoantibody against LSP was demonstrated in the serum of immunized B6 mice, but not in the sera of other strains after immunization. It was also found that EDTA contained in the buffer used for purification of LSP distinctly suppressed lymphocyte activity in vivo and in vitro. With the use of EDTA free LSP, it was shown that spleen cells of immunized B6 mice (especially of T cell enriched fraction) had a high reactivity studied by lymphocyte transformation test. Further examination showed that EDTA free LSP could induce mild liver lesions and lymphocyte reactivity against LSP, although neither histological change nor lymphocyte reactivity was found in the liver of B6 mice immunized with EDTA containing LSP.

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Selected References

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  1. Bartholomaeus W. N., Reed W. D., Joske R. A., Shilkin K. B. Autoantibody responses to liver-specific lipoprotein in mice. Immunology. 1981 Jun;43(2):219–226. [PMC free article] [PubMed] [Google Scholar]
  2. Büschenfelde K. H., Kössling F. K., Miescher P. A. Experimental chronic active hepatitis in rabbits following immunization with human liver proteins. Clin Exp Immunol. 1972 May;11(1):99–108. [PMC free article] [PubMed] [Google Scholar]
  3. Chisari F. V. Liver-specific protein in perspective. Gastroenterology. 1980 Jan;78(1):168–170. [PubMed] [Google Scholar]
  4. Cochrane A. M., Moussouros A., Smith A., Thomson A. D., Eddleston A. L., Williams R. Autoimmune reaction to a liver specific membrane antigen during acute viral hepatitis. Gut. 1976 Sep;17(9):714–718. doi: 10.1136/gut.17.9.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feighery C., McDonald G. S., Greally J. F., Weir D. G. Histological and immunological investigation of liver-specific protein (LSP) immunized rabbits compared with patients with liver disease. Clin Exp Immunol. 1981 Jul;45(1):143–151. [PMC free article] [PubMed] [Google Scholar]
  6. Hopf U., Meyer zum Büschenfelde K. H., Arnold W. Detection of a liver-membrane autoantibody in HBsAg-negative chronic active hepatitis. N Engl J Med. 1976 Mar 11;294(11):578–582. doi: 10.1056/NEJM197603112941103. [DOI] [PubMed] [Google Scholar]
  7. Hopf U., Meyer zum Büschenfelde K. H., Freudenberg J. Liver-specific antigens of different species. II. Localization of a membrane antigen at cell surface of isolated hepatocytes. Clin Exp Immunol. 1974 Jan;16(1):117–123. [PMC free article] [PubMed] [Google Scholar]
  8. Jensen D. M., McFarlane I. G., Portmann B. S., Eddleston A. L., Williams R. Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis. N Engl J Med. 1978 Jul 6;299(1):1–7. doi: 10.1056/NEJM197807062990101. [DOI] [PubMed] [Google Scholar]
  9. Kakumu S., Arakawa Y., Goji H., Kashio T., Yata K. Occurrence and significance of antibody to liver-specific membrane lipoprotein by double-antibody immunoprecipitation method in sera of patients with acute and chronic liver diseases. Gastroenterology. 1979 Apr;76(4):665–672. [PubMed] [Google Scholar]
  10. Kawanishi H., MacDermott R. P. K-cell-mediated antibody-dependent cellular cytotoxicity in chronic active liver disease. Gastroenterology. 1979 Jan;76(1):151–158. [PubMed] [Google Scholar]
  11. Köttgen E., Fabricius H. A., Stahn R., Gerok W. T-Lymphocyten-Aktivierung. Untersuchungen zur Funktion von Mediatorproteinen. Klin Wochenschr. 1981 Jun 15;59(12):669–674. doi: 10.1007/BF02593858. [DOI] [PubMed] [Google Scholar]
  12. Manns M., Meyer zum Büschenfelde K. H., Hütteroth T. H., Hess G. Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid-phase radioimmunoassay. Clin Exp Immunol. 1980 Nov;42(2):263–272. [PMC free article] [PubMed] [Google Scholar]
  13. McFarlane I. G., Wojcicka B. M., Zucker G. M., Eddleston A. L., Williams R. Purification and characterization of human liver-specific membrane lipoprotein (LSP). Clin Exp Immunol. 1977 Mar;27(3):381–390. [PMC free article] [PubMed] [Google Scholar]
  14. Meyer zum Büschenfelde K. H., Hopf U. Studies on the pathogenesis of experimental chronic active hepatitis in rabbits. I. Induction of the disease and protective effect of allogeneic liver specific proteins. Br J Exp Pathol. 1974 Oct;55(5):498–508. [PMC free article] [PubMed] [Google Scholar]
  15. Miller J., Smith M. G., Mitchell C. G., Reed W. D., Eddleston A. L., Williams R. Cell-mediated immunity to a human liver-specific antigen in patients with active chronic hepatitis and primary biliary cirrhosis. Lancet. 1972 Aug 12;2(7772):296–297. doi: 10.1016/s0140-6736(72)92904-2. [DOI] [PubMed] [Google Scholar]
  16. Ortona L., Laghi V., Cauda R., Nervo P. Immune response to rabbit liver-specific lipoprotein in acute viral hepatitis. Clin Exp Immunol. 1980 Dec;42(3):436–440. [PMC free article] [PubMed] [Google Scholar]
  17. Ortona L., Laghi V., Cauda R., Nervo P. Lymphocyte transformation test with rabbit liver specific lipoprotein (RLSP) in chronic active hepatitis. Clin Exp Immunol. 1979 Nov;38(2):231–234. [PMC free article] [PubMed] [Google Scholar]
  18. Scheiffarth F., Warnatz H., Mayer K. Studies concerning the importance of mononuclear cells in the development of experimental hepatitis. J Immunol. 1967 Feb;98(2):396–401. [PubMed] [Google Scholar]
  19. Tada T., Takemori T. Selective roles of thymus-derived lymphocytes in the antibody response. I. Differential suppressive effect of carrier-primed T cells on hapten-specific IgM and IgG antibody responses. J Exp Med. 1974 Jul 1;140(1):239–252. doi: 10.1084/jem.140.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Thestrup-Pedersen K., Ladefoged K., Andersen P. Lymphocyte transformation test with liver-specific protein and phytohaemagglutinin in patients with liver disease. Clin Exp Immunol. 1976 Apr;24(1):1–8. [PMC free article] [PubMed] [Google Scholar]
  21. Vogten A. J., Hadzic N., Shorter R. G., Summerskill W. H., Taylor W. F. Cell-mediated cytotoxicity in chronic active liver disease: a new test system. Gastroenterology. 1978 May;74(5 Pt 1):883–889. [PubMed] [Google Scholar]
  22. Warnatz H., Scheiffarth F., Schmeissner R. Studies on the cytotoxic effect of in vivo and in vitro immunized lymphocytes on liver target cells. Clin Exp Immunol. 1975 Aug;21(2):250–258. [PMC free article] [PubMed] [Google Scholar]

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