303. Further characterisation of lymphocyte-suppressing activity in gonadal fluids

Abstract

Protection of the developing gametes from an autoimmune response within the testis and ovary is essential for reproductive success, and autoimmune infertility represents a failure of this protection. The gonads also represent favorable sites for grafts of foreign tissue, that is, they are ‘immunologically privileged’. The actual mechanisms responsible for testicular and ovarian immune privilege are poorly understood. However, it has been well established that testicular interstitial fluid and ovarian fluid have profound inhibitory effects on T-cell activation and proliferation in vitro. We have established previously that a partially purified preparation of the inhibitor, isolated from bovine follicular fluid, suppresses proliferation in an in vitro T-cell activation assay, through induction of T-cell anergy and/or atypical apoptosis. Addition of increasing doses of normal fetal calf serum and/or bovine serum albumin blocks the actions of the inhibitor and progressively increases the ED₅₀ of the assay. It has also been shown that stimulating the T-cells with phorbol-12-myristate-13-acetate (PMA) in place of a polyclonal mitogenic stimulus such as phytohaemagglutinin bypasses the anergic effects of the inhibitor. These results suggest that the activity of the inhibitor may be negatively regulated in the circulation and tissues by serum-derived proteins and other factors. These data also indicate that the inhibitor’s activity is mediated through a specific cellular pathway, most likely involving protein kinase C isotypes, which are activated by PMA. Further work will delineate the molecular pathways and mechanisms of serum regulation of the gonadal lymphocyte-suppressing activity, which may be exploited in the treatment of autoimmune diseases and for prevention of transplant rejection.