Immune Privilege of the Testis: Meaning, Mechanisms, and Manifestations

The mammalian testis belongs among a small number of tissues that can unambiguously be called “immunologically privileged,” as demonstrated by the ability to tolerate not only testicular autoantigens but also alloand xenoantigens experimentally located within the testis environment. The mechanisms underlying this privilege remain poorly understood compared with more intensively studied models of immune privilege, such as the eye and feto-uterine unit, but evidently share key functional elements with these tissues. While physical structures like the blood-testis barrier have been implicated, antigen sequestration, aberrant lymphatics, or impeded immune cell access is not the underlying cause of testicular immune privilege, and it is increasingly evident that privilege involves active immunoregulation and local immunosuppression. More specifically, the unique somatic cells of the testis, the Sertoli cells of the seminiferous epithelium, and the steroidogenic Leydig cells, together with the large resident testicular macrophage population, have been directly implicated in suppressing or regulating immune responses to antigens located within the testicular environment. It is increasingly evident that these immunological control mechanisms also impinge upon, and may even participate in the regulation of, normal testicular function, spermatogenesis, and steroidogenesis. Conversely, failure of immune privilege is a significant cause of disease in the male tract, leading to chronic inflammation, infertility, and pain.