Infectious Diseases in Obstetrics and Gynecology 4:131-135 (1996) (C) 1996 Wiley-Liss, Inc. Immune Regulation in the Male Genital Tract Steven S. Witkin, Jan Jeremias, Ann Marie Bongiovanni, and M. Gladys Munoz2 1Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Cornel/ University Medical College, New York, New York; eDepartamento de Biologia de Organismos, Universidad Simon Bolivar, Caracas, Venezuela ABSTRACT Spermatozoa are not produced until puberty, long after the establishment of tolerance to self- antigens. Therefore, sperm-specific antigens are immunogenic in men. Most men, however, do not produce antibodies to their own gametes. Development of mechanisms to prevent or limit autoim- mune responses to spermatozoa were essential for preservation of reproductive capacity. Tight junctions between adjacent Sertoli cells, as part of the blood-testis barrier, prevent sperm-immune cell contact. In some portions of the genital tract this barrier is thin or incomplete. Immune mecha- nisms have evolved to actively suppress the autoimmune response to spermatozoa within the genital tract. Unlike in the circulation where CD4+ helper T lymphocytes predominate, CD8+ suppressor/ cytotoxic T lymphocytes are the most prominant T cells in the epididymis and vas deferens. In addition, spermatozoa suppress pro-inflammatory lymphocyte immune responses, possibly by induc- ing production of anti-inflammatory cytokines. Antisperm antibody production is induced in the male genital tract when a local infection or disruption in the genital tract physical barrier leads to an influx of CD4+ T cells. In response to induction of a productive immune response, two additional mechanisms downregulate humoral immunity within the genital tract. T lymphocytes possessing the / form of the antigen receptor (/ T cells) are concentrated in the male genital tract and in semen. These cells become activated and proliferate in men with evidence of sperm autoimmunity. Activated / T cells inhibit production of antibodies by activated B lymphocytes, thereby limiting antisperm antibody production. Heat shock proteins (hsps) are also present in semen in association with infection and antisperm antibody formation. Hsp gene transcription leads to inhibition of transcription of the genes coding for pro-inflammatory cytokines and, conversely, to activation of / T cells. Activated / T cells also promote hsp synthesis. The mechanisms to inhibit immunity to sperm may hinder effective immune elimination of microoganisms in the male genital tract. (C) 1996 Wiley-Liss, Inc. KEY WORDS / T lymphocytes, heat shock protein, antisperm antibodies, spermatozoa he immune system within the male genital tract has been subjected to unique evolutionary pressures. Spermatozoa are not produced until pu- berty, long after establishment of tolerance to self- antigens during the neonatal period. Therefore, sperm-specific antigens are immunogenic in men. The fact that the majority of men do not produce antisperm autoantibodies indicates the existence of Address correspondence to Dr. Steven S. Witkin, Department of Obstetrics and Gynecology, Cornell University Medical College, 515 East 71st Street, New York, New York 10021. Supported in part by NIH grant HD 33194 Article Received September 15, 1996 Accepted October I, 1996