Tissue microcircumstances for leukocytic infiltration into the testis and epididymis in mice

Spermatozoa do not appear in the seminiferous epithelium until puberty, when immune tolerance has already been established. Therefore, they contain various autoimmunogenic materials which are recognized as foreign by the self immune system. However, the testis and epididymis are known as immunologically privileged organs. In particular, the blood-testis barrier (BTB) formed by Sertoli cells and the blood-epididymal barrier formed by epididymal epithelial cells protect autoimmunogeneic spermatozoa from attack by the self immune system. The immune privileged circumstances in the testis and epididymis have been demonstrated by many studies to involve a local transplantation system. We review here the immune privileged status of these organs from the viewpoint of induction of inflammatory cell responses in mice. The testicular interstitium in mice is resistant to vasculitis, lymphangitis, spermatic granuloma and polymorphonuclear cell infiltration: however, the epididymal interstitium is vulnerable to them. Therefore, the testicular tissue outside BTB is also protected from inflammatory cell infiltration, although many resident macrophages are normally present in the testis. In sharp contrast, subcutaneous injection of viable syngeneic testicular germ cells (TGC) alone induces autoimmune orchitis with no involvement of the epididymitis in mice. In the testes of TGC-immunized animals, severe lymphocytic infiltration with aspermatogenesis was seen in spite of no use of adjuvants. Unexpectedly, injections of viable epididymal spermatozoa (ES) did not evoke any autoimmune inflammation in the epididymides. Therefore, the testis rather than the epididymis may easily become an unprivileged organ as to autoimmunity under some special conditions.