Immunology of the testis and excurrent ducts

Abstract

Immune cells are regular components of the male reproductive tract of mammals, including humans. Whereas interactions between the testis and the immune system have been a source of considerable curiosity and remained obscure for many years, there is now compelling evidence that testicular immune cells play a key role in testicular function. Located in the interstitial compartment of the normal, unaffected testis they are implicated in the mechanisms that make the testis an immunologically privileged site where germ cells are protected from autoimmune attack and foreign tissue grafts may survive for extended periods. With regard to normal development and function of the testis, both pro- and anti-inflammatory cytokines are involved in the complex interactions between testicular somatic cells and resident as well as circulating immune cells. The same cytokines experience considerable upregulation during the induction and amplification of cellular immune responses, illustrating that the testicular environment does not preclude inflammatory reactions and subsequent disturbance of spermatogenesis and steroidogenesis. Notably, active immunization with testicular tissue or adoptive transfer of specific T lymphocytes causes autoimmune orchitis in experimental animals. In men, infection and inflammation of the reproductive tract including the testes are widely accepted as important aetiological factors of infertility. Whereas symptomatic orchitis due to bacterial or viral infections is considered to be rare, a high prevalence of asymptomatic testicular inflammatory reactions is observed among infertile males. Immune cells including macrophages, mast cells and lymphocytes are also encountered in the interstitial and peritubular tissue of the epididymis and excurrent ductal system. In contrast to the seminiferous epithelium, however, macrophages and lymphocytes are observed within the epithelium, the majority of lymphocytes being CD8+ T cells. Obviously, separation of germ cell-related antigens and immune cells is not as stringent in the excurrent ducts as in the testis, but the mechanisms of local immunoregulation remain unclear. With regard to immune activation and recruitment of inflammatory cells, the epididymis appears to be more susceptible than the testis. Insults such as vasectomy are associated with a high risk of formation of antisperm antibodies. In conclusion, immunopathological reactions in the testis and excurrent ducts should not be neglected as an underlying reason for, or co-factor of, male infertility. Further investigation of the mechanisms that regulate testicular and epididymal immune functions in health and disease may encourage the search for appropriate diagnostic and therapeutic strategies for male infertility. © 2006 Springer-Verlag Berlin Heidelberg.