Patterns of MHC antigenic modulation in cyclosporine-induced autoimmunity. Implications for pathogenesis

To explore the role of aberrant MHC expression in the pathogenesis of cyclosporine-induced autoimmunity (CSIA), we examined the patterns of major histocompatibility complex (MHC) class I and II antigenic modulation during disease induction and the relationship between MHC modulation and tissue injury. Disease was induced consistently in rats but never in mice. Unlike rats, mice were resistant to downmodulation by cyclosporine of class II antigen expression in the thymic medulla. In rats with CSIA, MHC class I and II antigen expression was induced on all target epithelia, frequently before mononuclear infiltration or tissue injury, consistent with a role for MHC antigens in selecting cells for injury. Much increased numbers of strongly class II-positive interstitial dendritic cells were present throughout the body, even in tissues not involved by CSIA. Thus, class II expression alone is insufficient to lead to cell injury in CSIA.