ABSTRACT
Experimental autoimmune hepatitis (EAH) has been induced in several strains of mouse by immunization with liver cytosol plus Freund's complete adjuvant. Our goal was to validate EAH in female C57Bl/6 mice and to compare the ability of immunization with liver cytosol and hepatocyte plasma membranes in Freund's complete (CFA) or incomplete (IFA) adjuvants to induce EAH. Control mice received Hank's balanced salt solution (HBSS), alone or an emulsion of HBSS in either CFA or IFA. The severity of hepatitis in coded liver sections was compared. EAH-like lesions were found not only in mice immunized with liver antigens in CFA or IFA but also in mice injected with either CFA or IFA. Mice injected with HBSS alone showed no hepatitis. These results indicate that immunization with neither liver nor mycobacteria cell wall antigens is required for induction of EAH-like lesions and suggest that the EAH in C57Bl/6 mice may be a nonspecific inflammatory response to adjuvant oil.
Subject(s)
Autoimmune Diseases/pathology , Freund's Adjuvant/toxicity , Hepatitis, Animal/pathology , Animals , Autoimmune Diseases/immunology , Cell Membrane/immunology , Female , Freund's Adjuvant/immunology , Hepatitis, Animal/immunology , Injections, Intraperitoneal , Injections, Subcutaneous , Liver/immunology , Liver/pathology , Mice , Mice, Inbred Strains , Oils , ParaffinABSTRACT
Murine chronic graft-vs-host disease (CGBHD) to minor histocompatibility antigens (B10.D2----BALB/c) is characterized by inflammatory destruction of intrahepatic bile ducts, scleroderma-like skin lesions, and lymphoid involution. Spleen cells isolated from this model proliferate poorly when stimulated with mitogens. Previous reports indicate defective lymphocyte proliferation in this model is the result of active suppression induced by the graft-vs-host reaction in the spleen and is mediated by Thy 1.2-, sIg-, plastic nonadherent, splenic natural suppressor (NS) cells. To determine whether the intense CGVHD in the liver is associated with induction of suppression, we compared the suppressor activity of hepatic and splenic mononuclear inflammatory cells isolated concurrently during murine CGVHD. Both hepatic and splenic MC suppressed the proliferation of mitogen-stimulated normal spleen cells in a non-MHC, non-Mls restricted manner. T cells contributed to the suppressor activity of both populations. However, the suppressor activity of hepatic MC was mediated largely by a macrophage-enriched population of MC while that of splenic MC was mediated largely by NS cells.
