Defective suppressor function of spleen cells by neonatal thymectomy and persistence of experimental auto‐immune hepatitis in mice

Abstract

The effects of neonatal thymectomy on a model of auto‐immune hepatitis prepared by immunizing A/J mice with syngeneic crude liver proteins were studied. Hepatitis was more severe in neonatally thymectomized mice (Group B) than in non‐thymectomized controls (Group A). Changes in the hepatic lobules were reduced in both groups 3 months after the final immunization, but inflammation around the portal areas tended to persist in Group B; only this group showed frequent infiltration of mononuclear cells accompanied by destruction of the limiting plate in the portal area. The serum level of auto‐antibody to liver‐specific membrane lipoprotein complex (LSP) and delayed‐type hypersensitivity (DTH) to LSP were higher in Group B than in Group A. The auto‐antibody to LSP was positive in both groups 3 months after the final immunization. Although it was significantly reduced in Group A compared with the level 3 days after the final immunization, it remained high in Group B. Liver damage, production of the auto‐antibody to LSP and DTH to LSP were reduced by adoptive transfer of normal murine spleen cells, but the spleen cells of neonatally thymectomized mice showed no such effects. These results suggest that normal spleen cells possess the capability of suppressing auto‐immune hepatitis, and the defect of this capability due to T‐cell dysfunction by neonatal thymectomy contributes to the promotion and persistence of auto‐immune hepatitis.