Induction of class II major histocompatibility complex antigen expression in human granulosa cells by interferon gamma: a potential mechanism contributing to autoimmune ovarian failure.
We investigated the possibility that major histocompatibility complex (MHC) class II antigens and interferon gamma, a product of activated T lymphocytes, play a role in human autoimmune oophoritis. MHC class II molecules initiate immune responses by presenting antigens to T-helper lymphocytes; interferon gamma can induce class II antigen expression at ectopic sites and has been implicated in the cause of various autoimmune disorders. We studied the expression of class II MHC antigens in ovaries from normal women of reproductive-age and from women with premature autoimmune ovarian failure. Immunoperoxidase technique applied to tissue sections of nine normal human ovaries revealed class II MHC antigen expression only on occasional cells of macrophage morphology; granulosa cells were negative regardless of stage of follicular maturation. In contrast, extensive and intense class II antigen expression was observed in granulosa cells in ovarian biopsy sections from four patients with premature autoimmune ovarian failure. Immunofluorescence and radioimmunoassay techniques used to detect and quantitate MHC antigens revealed that class II antigen expression could be induced and class I MHC antigen expression was enhanced in granulosa cell cultures after the addition of interferon gamma. These data provide evidence that autoimmune oophoritis is associated with ectopic expression of MHC class II antigens by ovarian granulosa cells, and that this phenomenon can be induced by the immunologic cytokine interferon gamma.