Administration of interleukin-2 induces major histocompatibility complex class II expression on the biliary epithelial cells, possibly through endogenous interferon-γ production

Abstract

In various organ‐specific autoimmune diseases, aberrant expression of major histocompatibility complex class II antigens on each target epithelial cell has been reported. Some researchers have attempted to link this phenomenon to the antigen‐presenting capacity and the induction of autoimmunity, whereas others think it might serve as a peripheral mechanism for the induction and the maintenance of self‐tolerance in autoreactive T cells. In this study, we showed that intraperitoneal administration of interleukin‐2 (1.2 × 10⁶ IU/kg) to 4‐wk‐old male BALB/c mice for 35 consecutive days induced lymphocyte infiltration around bile ducts in the liver and major histocompatibility complex class II expression on biliary epithelial cells, which was immunoelectron microscopically confined to the luminal cell surface. Immunohistochemically, lymphocytes accumulating around bile ducts were mainly T cells, positive for CD3, L3T4 and H‐2 class II molecules, and a few of them were positive for Lyt‐2 and negative for immunoglobulin. Half of the infiltrates were positive for asialo GM₁, and one‐third was positive for interferon‐γ, Interferon‐γ–positive, L3T4‐positive cells were detected in mirror sections. However, neither the destruction of biliary epithelial cells nor the presence of granulomas was observed. Autoantibodies were serologically undetectable. The existence of interferon‐γ–positive cells in the lesion and the fact that intravenous administration of anti–interferon‐γ twice a week completely inhibited the lymphocyte infiltration and the major histocompatibility complex class II expression on biliary epithelial cells suggested that these changes were induced through endogenous interferon‐γ production. As a result, we made it possible to induce the aberrant expression of class II on biliary epithelial cells in vivo and propose that the aberrant major histocompatibility complex class II expression of itself cannot trigger autoimmune reactions, such as those leading to the destruction of biliary epithelial cells, in this strain. (HEPATOLOGY 1992;16:409–417.)