Human Reproduction Update, Vol.1, No.1 pp.35-50, 1995
© © Oxford University Press
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Mechanisms of autoimmune disease in the testis and ovary
1Department of Pathology, University of Virginia Charlottesville, VA 22908 2Department of Microbiology, Brigham Young University Provo, UT 84602, USA
To whom correspondence should be addressed at: 1To whom correspondence should be addressed
This article reviews recent research on autoimmune diseases of the testis and ovary based on two experimental approaches for induction of autoimmune diseases of the gonads (immunization with testis or ovary antigen, usually with adjuvant, and deliberate alteration of the immune system in normal animals, without injecting antigen or adjuvant). It has been found that the local testicular immunoregulatory environment partially impedes autoimmune responses to on-togenic testis antigens and regulatory T cells usually control pathogenic T cells that are found in the normal peripheral immune system. If the clonal balance of these CD4+ T cell subsets is tipped in favour of pathogenic T cells, autoimmune diseases of the gonads could ensue. Loss of regulatory T cells may occur through aberrant T cell development, or oophoritogenic T cells can be activated by non-ovarian peptides that cross-react with self peptides at the level of the T cell receptor. The inflammatory CD4 (Thl) T cell mechanism has been established to be a critical pathway for auto-immune orchitis and autoimmune oophoritis; tumour necrosis factor has been shown to be required for amplification of the pathogenic T cell response. Histopa-thology has suggested tissue locations wherein pathogenic T cells encounter testicular and ovarian target antigens. Antibodies bind to both testicular and ovarian target antigens during the development of autoimmune orchitis and autoimmune oophoritis, but the precise role of the antibodies has not been determined. Resolution of this role may influence the clarification of the mechanism whereby autoantibody may access ejaculated human spermatozoa to cause infertility and the future of contraceptive vaccine development based on ovarian antigens. A novel mechanism of autoantibody induction and an immunogenetic approach to autoimmune oophoritis and orchitis, based on molecular linkage analysis of inbred mice, are also reviewed.
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