Research on murine autoimmune ovarian disease (AOD) models suggests that the following sequence of events operate in prevention and induction of AOD. Potentially pathogenic T cells for oocyte antigens that exist in normal mice are kept in check by regulatory CD25+ T cells. Oocyte-specific pathogenic T cells are activated when the regulation is lost, as after day 3 thymectomy, or when T cells are stimulated through molecular mimicry. Activated, proinflammatory T cells induce interstitial ovarian inflammation without disruption in ovarian function. Activated T cells also help B cells that respond to endogenous oocyte antigens, to produce oocyte autoantibodies of diversified specificities. Autoantibodies, nonpathogenic in themselves, retarget T cell-mediated inflammation to ovarian follicles resulting in ovarian atrophy and ovarian failure. Future studies should determine the applicability of these findings to human ovarian autoimmunity.
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