I will continue to investigate the pathogenesis of experimental autoimmune orchitis (EAO) in the mouse as a probable cause of male infertility and a complication of anti-fertility vaccines. Recent findings that have helped to formulate this proposal include (a) identification of mouse strains susceptible and nonsusceptible to EAO, (b) development to testis antigen specific T cell proliferative response (LPR) assay, (c) systemic transfer of EAO to untreated recipients by immune delayed hypersensitivity or helper/inducer T cells, (d) identification of suppressor cells in lymph node cells that normally prevent LPR and adoptive transfer of EAO, (e) differences in immunopathology of EAO by passive transfer versus active immunization with respect to orchitis distribution and IgG deposition in or adjacent to Sertoli cells (""""""""Sertoli cell IgG) that occurs before orchitis onset and can be transferred to pertussis treated mice with anti-testis antiserum, and (f) mapping of Ia positive cells in normal testes and those during EAO induction. To study the functional phenotype of the lymphocytes responsible for adoptive transfer of EAO, I will compare subpopulations isolated by specific monoclonal antibodies, study testis specific T cell lines and clones with defined functional phenotypes, and compare T cell lines from susceptible an nonsusceptible BALB/c substrains. To study the mechanism of immunoregulation against testicular autoimmunity, I will identify functional suppressor cells in mice with EAO, in mice immunized with testis in incomplete adjuvant, and in nonresponder mouse strains, then characterize these cells with respect to phenotype, antigen-specificity, and requirements of endogenous antigens for induction and maintenance. To study the mechanism of EAO initiation by delining the cause for differences in active and passive EAO, I will determine hether anti-testis antibody and/or pertussis toxin influence the localization of orchitis of labeled T cell lines in testes with or without """"""""Sertoli cell IgG"""""""", and study phagocytic functions of Sertoli cells. I will examine the distribution and existence of target antigens outside the blood- testis barrier by in situ localization and study of antigen presenting capacity of testicular dendritic cells. Finally, to study the role of humoral antibody, we will identify the specificity and localization of """"""""Sertoli cell IgG.""""""""
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