Autoimmune ovarian disease: mechanism of induction and prevention.
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.
Department of Pathology, University of Virginia, Charlottesville, Virginia 22908, USA. kst7k@virginia.edu
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D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008562:Membrane Glycoproteins / Q000276:immunology; D010049:Ovarian Diseases / Q000276:immunology* / Q000517:prevention & control*; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000276:immunology; D000072216:Zona Pellucida Glycoproteins
D001323:Autoantibodies; D001324:Autoantigens; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins