Experimental hepatitis in neonatally thymectomized mice: Transfer of disease and the role of T cells

Using neonatally A/J thymectomized mice, we have produced chronic hepatitis by administration of sublethal doses of Propionibacterium acnes and lipopolysaccharide (LPS). Our goal in this unique model was to evaluate the effector cell. population required to generate chronic hepatitis by transferring spleen cells or splenic subpopulations derived from donor thymectomized mice with chronic hepatitis into congenic recipient nonimmunized thymectomized or sham-thymectomized animals. Several key observations were made regarding the ability to induce and to transfer disease. First, an inflammatory liver injury in neonatally thymectomized (NTx) mice was readily generated using sublethal doses of P. acnes and LPS. Second, the lesions were persistent and associated with the production of autoantibodies to liver-specific lipoprotein and anti-nuclear antibodies. Third, these features were not found in comparably injected nonthymectomized control A/J mice. Fourth, the same liver injury was transferred to neonatally thymectomized but otherwise naive mice by the transfer of donor spleen cells from affected mice previously induced to develop experimental hepatitis. Fifth, the transfer of this liver injury could not be achieved using T-cell-depleted spleen cells. Deletion of CD4(+) T cells or CD8(+) T cells by sensitized spleen cells resulted in suppression of the transferred liver injury. In contrast, transfer of nylon wool adherent splenic T cells induced severe hepatitis. These data suggest that the chronic liver injury induced in NTx mice by administration of P. acnes and LPS involves a breakdown in tolerance accompanied by the appearance of autoantibodies and that nylon wool adherent CD4(+) and CD8(+) T cells play important roles in the modulation of liver injury. (C) 1997 Academic Press.