Evidence for spontaneous immunosuppression in autoimmune hepatitis



Autoimmune hepatitis (AIH) runs a variable clinical course. Slow disease progression or even spontaneous remissions can be observed and suggest that the autoimmune process can, at least to a certain extent, be controlled by regulatory elements of the patient's own immune system. In experimental autoimmune hepatitis (EAH) spontaneous recovery is regularly observed and associated with antigen-specific and antigen-nonspecific suppression. The aim of the current study was to search for similar immunoregulatory phenomena in patients with AIH. We examined T-cell reactivity to soluble human liver antigens in 11 patients with active autoimmune hepatitis and 30 patients with other liver diseases (chronic viral hepatitis, primary biliary cirrhosis, fatty liver). T-cell reactivity to liver antigens was almost exclusively confined to the AIH patients. In 9 of these 11 patients we were able to compare the T-cell response in active untreated disease, directly after initiation of immunosuppressive therapy and in remission, at which point T-cell reactivity was found to be markedly reduced. Addition of irradiated peripheral blood cells from the active disease phase or the remission phase to the responding cells taken before treatment showed that in eight of the nine patients there was marked suppression of the liver-specific T-cell response by cells from the remission phase. Study of the in vivo immune responsiveness by giving a tetanus toxoid booster immunization to nine patients with active untreated AIH as well as healthy controls and patients with other liver diseases showed that none of the patients with AIH showed a response to the tetanus immunization, whereas almost all the other patients showed marked responses. Taken together these results show the presence of active suppression of T-cell autoreactivity in vitro in AIH and marked nonresponsiveness to in vivo challenge with an unrelated antigen, suggesting generalized spontaneous immunosuppression that is more pronounced in vivo than what can be measured in vitro. Spontaneous immunosuppression, however, is not sufficient to effectively suppress the disease process. Immunosuppressive therapy is required for remission induction, but is apparently helped by the patient's own immunoregulatory activity. These observations support the concept of peripheral control mechanisms being operative in patients with AIH, and these could be the basis for a more effective and specific immunotherapy of this condition in the future. (Hepatology 1995;22:381–388.)