Immune Regulation in the Male Genital Tract

[摘要] 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 notproduce antibodies to their own gametes. Development of mechanisms to prevent or limit autoimmuneresponses to spermatozoa were essential for preservation of reproductive capacity. Tightjunctions between adjacent Sertoli cells, as part of the blood-testis barrier, prevent sperm-immunecell contact. In some portions of the genital tract this barrier is thin or incomplete. Immune mechanismshave evolved to actively suppress the autoimmune response to spermatozoa within the genitaltract. Unlike in the circulation whereCD4+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 inducingproduction of anti-inflammatory cytokines. Antisperm antibody production is induced in themale genital tract when a local infection or disruption in the genital tract physical barrier leads toan influx ofCD4+T cells. In response to induction of a productive immune response, two additionalmechanisms downregulate humoral immunity within the genital tract. T lymphocytes possessingthe γσ form of the antigen receptor (γσ T cells) are concentrated in the male genital tract and insemen. These cells become activated and proliferate in men with evidence of sperm autoimmunity.Activated γσ T cells inhibit production of antibodies by activated B lymphocytes, thereby limitingantisperm antibody production. Heat shock proteins (hsps) are also present in semen in associationwith infection and antisperm antibody formation. Hsp gene transcription leads to inhibition oftranscription of the genes coding for pro-inflammatory cytokines and, conversely, to activation ofγσ T cells. Activated γσ T cells also promote hsp synthesis. The mechanisms to inhibit immunityto sperm may hinder effective immune elimination of microoganisms in the male genitaltract.

[学科分类] 妇产科学