MALE GENITAL TRACT IMMUNITY mechanisms to limit immune responsiveness in the male genital tract. This communication will detail the various means both passive and active by which productive immunity is impaired at this site. This subject has been reviewed previously1,z. BLOOD-TESTIS BARRIER The first line of defense against sperm-specific au- toimmunity is anatomical, the blood-testis barrier. A tight network of intercellular junctions between Sertoli cells retards the passage of sperm-related macromolecules and cells out of, and immune com- ponents into, the testis3. This physical barrier is narrow in some regions and is not completely effec- tive in preventing an interaction between intra and extra- genital tract components. In mice, T lympho- cytes that had been sensitized to spermatozoa and subsequently transferred to recipient males, gained access to the genital tract and reacted with sperm autoantigens4. In addition, the integrity of the geni- tal tract can be compromised as a consequence of testicular trauma, inflammation of infectious or non- infectious origin, congenital anomoly or due to the deliberate severing of the vas deferens (vasectomy). SUPPRESSION OF IMMUNE RESPONSES The T lymphocytes that recognized sperm autoan- tigens in the study cited above were CD4+ cells. These lymphocytes do not react with native anti- gens. Only those antigens that have been digested and subsequently transported and presented on the surface of an antigen-presenting cell (APC) in asso- ciation with class 2 major histocompatibility (MHC) molecules can be recognized by the CD4+ cell. Macrophages, one of the major APC, are present in the male genital tract4. In their resting state, macrophages do not normally express MHC class 2 antigens. However, interferon gamma (IFN/), a product of activated T cells, is a potent inducer of MHC class 2 antigen expression on macrophagess. Therefore, one means of inhibiting immune re- sponses within the genital tract would be to prevent IFN/production. Evidence exists for several mechanisms that in- hibit pro-inflammatory, IFN/-producing immune responses in the male genital tract. Detailed immu- nohistological studies of the human male genital tract, summarized by E1-Demiry and James6, dem- onstrated the predominance of T lymphocytes with the suppressor/cytotoxic phenotype (CD8) within 132 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY WITKIN E T AL. the epithelium and lamina propria of the vas defer- ens, epididymis, and rete testis. Macrophages were also identified at these same sites as well as between the seminiferous tubules. The authors noted the accumulation of CD8+ T cells in those regions of the tract where the blood-testis barrier were weak- est and hypothesized that CD8+ cells may function to actively suppress immune responses to sperm- specific antigens. In marked contrast, CD4+ T cells predominated in both the genital tract and in se- men in men with evidence of autoimmunity to sperm. Mononuclear cells present in human semen were also shown to function as suppressor cells in vitro8. Further evidence for an active suppression of sperm-directed immune responses comes from studies in mice. Neonatal thymectomy resulted in the subsequent development of orchitis in a process prevented by the infusion of spleen-derived lym- phocytes from untreated controls9. SPERM-INDUCED IMMUNE SUPPRESSION Purified human spermatozoa, when incubated in vitro with peripheral blood mononuclear cells, in- duce neither lymphocyte proliferation nor the syn- thesis of IFN/. In contrast, sperm with bound auto- antibodies are potent IFN/ inducers 1. Similarly, circulating IFN/was identified in sera of women whose husbands had sperm autoimmunity but not in sera from women whose serum were antibody- free 11. Spermatozoa appear to actively suppress im- mune responses. Intravenous injection of spermato- zoa or testicular germ cells into syngeneic mice profoundly suppressed subsequent immunity by a mechanism involving activation of suppressor T cells z’3. Rectal insemination of semen into rabbits led to similar consequences 14. Similarly, purified, living ejaculated human spermatozoa inhibited in vitro lymphocyte proliferative responsesI5. A failure in sperm-induced immune suppression by their male partners’ semen has also been associated with antisperm antibody formation in the female sexual partners. 15. Recent evidence from our laboratory in- dicates that human spermatozoa induce the produc- tion of anti-inflammatory cytokines by lymphoid cells (in preparation). / T LYMPHOCYTES Recently, T lymphocytes possessing a T cell recep- tor heterodimer complex composed of / and