Interactions between the immune system and the ruminant conceptus

Abstract

Interactions of the conceptus with the immune system can involve either anti-sperm or anti-conceptus immune responses that limit the success of pregnancy of beneficial effects of cytokines released from lymphoid cells on embryonic growth and gene expression. The immune system is functional in the uterus and therefore there is the potential for anti-conceptus immune responses. However, endometrial lymphocytes are distinct in many respects from lymphoid cells at peripheral sites; one major subpopulation expresses the gamma delta T-cell receptor and may not recognize major histocompatibility antigens. There are also several control systems to limit anti-conceptus immune responses. In particular, expression of major histocompatibility antigens on the trophoblast is either absent or of limited distribution. In addition, activation of anti-conceptus immune responses leading to cytolytic responses is further limited by the presence of molecules that can inhibit lymphocyte transformation. The most well-characterized of these are prostaglandin E2 from placental and endometrial tissues, interferon-tau from the trophoblast during early pregnancy, and two endometrial proteins called the uterine milk proteins (UTMP). Progesterone plays a central role in inhibition of immune responses in actions that are mediated at least in part through endometrial secretion of UTMP. Cytokines play important roles as autocrine and paracrine regulators in many tissues including the reproductive tract. In ruminants, the best described example is interferon-tau. Other cytokines found in the reproductive tract or produced by the conceptus include interleukin-1, leukaemia inhibitory factor, granulocyte-macrophage colony stimulating factor and interleukin-6. It is possible that the major source of cytokines in the reproductive tract is non-lymphoid cells of the endometrium and trophoblast. It is not known to what extent endometrial lymphocytes contribute to the cytokine milieu because no cytokine has been identified as a product of endometrial lymphocytes. However, there is a population of granulated lymphocytes that increase in number and granularity in the luminal epithelium of the late-pregnant ewe that is a potential source of cytokines.