Remission of experimental autoimmune hepatitis is associated with antigen-specific and non-specific immunosuppression

Abstract

Experimental autoimmune hepatitis (EAH) is an animal model for autoimmune hepatitis. The disease is T cell-mediated and runs a subacute course, with maximal disease activity around week four after disease induction and a slow ensuing recovery. The aim of the present study was to investigate the immunoregulatory mechanisms that may account for recovery in EAH. It was found that T cell reactivity to liver antigens preceded histological disease, but at the peak of disease activity this T cell response was already suppressed. Active and antigen-specific suppression could be demonstrated, as irradiated splenocytes from animals at the beginning of recovery from EAH were able to suppress in vitro the T cell response to liver antigens by 42%. The response to an irrelevant antigen was suppressed by 16%, showing additional antigen non-specific suppression in vitro. The response to an in vivo immunization with an unrelated microbial antigen (tetanus toxoid) at the peak of disease was markedly reduced (by 90%). These data demonstrate in vitro and in vivo immunosuppression associated with the overcoming of and recovery from EAH. They stress the importance of immunoregulatory cycles in the control of autoimmune hepatitis.