The Immune Privilege of the Testis

Male germ cells (GC) enter meiosis beginning their complex transition into highly specialized spermatozoa at the time of puberty, after the establishment of immune competence. During the process, a myriad of surface and intracellular proteins are expressed, yet these new autoantigens are tolerated by the testis. The immunogenicity of the proteins is not diminished, as shown by their ability to induce strong autoimmune reactions when injected elsewhere in the body [1, 2] ; rather it is the testis itself that confers protection. Initial suggestions that the testis was an immune privileged site were substantiated experimentally when histoincompatible alloand xenografts placed into the interstitial space of the rat testis survived and prospered for an indefi nite period of time [3] . Similarly, ectopically transplanted allogenic Sertoli cells (SC) not only survive, but when co-transplanted with allogenic pancreatic islets, also resist rejection without additional systemic immunosuppression in animals [4] . More recently, the transplantation of spermatogonia in germ cell depleted testis could restore spermatogenesis even across species borders in some instances [5] . There is general agreement that immune privilege is an evolutionary adaptation to protect vulnerable tissues with limited capacity for regeneration, thereby avoiding loss of function [6, 7] . For the testis this means safeguarding reproductive capability. Notwithstanding its immune privileged status, the testis is clearly capable of mounting normal infl ammatory responses, as proven by its effective response to viral and bacterial infection. In pathological circumstances, the misbalance between the tolerogenic and the efferent limbs of the testicular immune response can lead to the formation of autosperm antibodies and in rare instances, autoimmune epididymo-orchitis in humans. Immune infertility is now estimated to be a considerable cause of sterility in couples seeking medical assistance [8– 12] . The most commonly used model for the investigation of autoimmune-based infl ammatory testicular impairment is experimental autoimmune orchitis (EAO), a rodent model