Immune privilege and inflammation of the testis – lessons from the infertile male

Immune cells are regular components of the testis and likely to participate in the complex local regulation of testicular function. Studies in experimental animals indicate that the testis is an immunologically privileged site where germ cell antigens are protected from autoimmune attack and foreign tissue grafts may survive for extended periods. However, the testicular environment does not preclude immune activation resulting in inflammatory reactions. Active immunization with testicular tissue or adoptive transfer of specific T lymphocytes causes autoimmune orchitis. Whereas symptomatic orchitis due to viral or bacterial infections is considered to be rare in man, recent studies among infertile males revealed a high prevalence of asymptomatic testicular inflammatory reactions associated with impaired spermatogenesis. Notably, the infiltration of T lymphocytes into the testis reflects disturbance of the delicate local immunoregulation. Both predominant peritubular localization of lymphocytes and characteristic morphological changes of the seminiferous tubules support the concept that activation of autoreactive T cells inducible by various etiological factors including noninfectious agents is involved. With regard to localization and functional polarization of T lymphocytes, adhesion molecules as well as chemokines and their receptors have to be considered as crucial components. In conclusion, immunopathological reactions in the testis should not be neglected as underlying reason or cofactor of male infertility. Further investigation of the mechanisms that regulate testicular immune functions in health and disease may encourage the search for appropriate therapeutic strategies such as specific immunomodulation.