Autoimmune ovarian inflammation triggered by proinflammatory (Th1) T cellsis compatible with normal ovarian function in mice

The detection of noninfectious ovarian inflammation (oophoritis) and serum ovarian autoantibodies in a patient with premature ovarian failure is indic ative of an autoimmune etiology, The mechanisms of autoimmune ovarian injur y leading to loss of function are currently unknown. In this study we inves tigated the impact of oophoritis on ovarian function based on two murine au toimmune ovarian disease (AOD) models. AOD can be induced by thymectomy at Day 3 after birth (d3tx). D3tx mice develop ovarian inflammation and atroph y with loss of oocytes. In these mice, ovarian atrophy and not oophoritis c orrelated with abnormal estrous cyclicity. The second AOD model is induced by active immunization of adult mice with a murine ZP3 peptide (pZP3) in ad juvant. After active immunization, the zona pellucida antibody titer, not o ophoritis, correlated with reduced fertility. To investigate the effect of oophoritis in the absence of antibody response or ovarian atrophy, pZP3-spe cific T cells were passively transferred into naive syngeneic mice. This re cruited cytokine-producing cells into the ovaries so that elevated cytokine production and its effect on ovarian function could be examined. Recipient s of pZP3-specific T cells developed severe granulomatous oophoritis, and t he diseased ovaries had elevated ovarian mRNA levels of interferon-gamma, i nterleukin-1 beta, and tumor necrosis factor alpha. Despite these changes, fertility rates and gonadotropin-induced follicular development remained es sentially normal. Therefore, normal ovarian function is compatible with sev ere ovarian inflammation mediated by autoreactive T cells.