Control and impairment of immune privilege in the testis and in semen.

It has long been known that the testis is an immunologically privileged site in the body, and that human seminal plasma possesses a generalized immunosuppressive activity. Multiple factors participate in the establishment of immunotolerance in the testis: the blood-tubular barrier; the local production of immunosuppressive molecules by Sertoli cells; and the Fas system as regulator of immunological homeostasis in both physiological and pathological conditions. Cytokine-induced up-regulation of Fas as well as of integrin ligands, which are known to be specific binding molecules for lymphocytes on the Sertoli cell surface, indicates that the 'nursing' cells of seminiferous epithelium might be important in the impairment of immune privilege, causing autoimmune orchitis. In addition, the soluble form of Fas-ligand protein present in the seminal plasma of infertile patients might suggest a role for this immunomodulatory protein in male infertility. Finally, an understanding of the mechanisms underlying immune privilege in the testis and in semen might help to clarify how cells expressing 'non-self' antigens (such as male gametes) can escape the immune system in both the male and female genital tracts.

Testicular FasL is expressed by sperm cells.

The testis is the main source of Fas ligand (FasL) mRNA in rodents; it is generally believed that this molecule, expressed on bordering somatic Sertoli cells, bestows an immune-privileged status in the testis by eliminating infiltrating inflammatory Fas-bearing leukocytes. Our results demonstrate that the attribution of testicular expression of FasL to Sertoli cells is erroneous and that FasL transcription instead occurs in meiotic and postmeiotic germ cells, whereas the protein is only displayed on mature spermatozoa. These findings point to a significant role of the Fas system in the biology of mammalian reproduction.