Concerning the immunology of the uterus

As a mucosal organ, the uterus is unique in being subject to exposure to three types of antigen: 1) chronically to micro-organisms, 2) episodically to sperm bearing both auto- and alloantigens as well as soluble antigens in seminal plasma, and 3) to conceptuses - nature's allografts - expressing transplantation antigens. That the uterus is effective in handling pathogens is evidenced by the rarity of infections. Local macrophages, immunocytes, and a secretory immune system, most evident in the cervix, probably underlie this attribute. Mammals' reproductive success hints that the uterus is immunologically discriminating toward the nonharmful but biologically important antigens of classes 2 and 3. Why sperm are not normally destroyed immunologically in the female prior to fertilization and why conceptuses are not rejected are central unresolved questions in reproductive immunology. Undoubtedly, important immunoregulatory principles are operating in this remarkable organ and its decidua. Better to understand antigenic exposure in the rat uterus, we have reinvestigated its lymphatic drainage using labeled cell injection and microanatomical procedures. Despite abundant lymphatics in the myometrium, cells placed in the uterine lumen did not readily gain access to the lymphatic system. There was a paucity of lymphatics in the endometrium, but Ia-positive dendritic cells were abundant. Soluble antigen exposure via the uterus failed to evoke a primary antibody response yet did prime the host for a secondary response. This restriction of systemic antigen presentation from the uterus, in conjunction with both cellular and noncellular immunoregulatory principles acting locally, may be important to ensure maternal hyporesponsiveness to paternal alloantigens.