The role of regulatory T Cells in autoimmune orchitis

Regulatory T cells (Tregs) mediate tolerance to self-antigens maintaining immune homeostasis. Defects in the number and function of Tregs lead to aberrant immune responses to autologous components, thereby causing autoimmune diseases. Male infertility as a result of immune testicular damage follows through auto-reactive T-cell activation by antigens or pathogens that disrupt testis tolerance mechanisms. In this review we summarise the main evidence on Treg behaviour in inflammatory testicular pathologies focusing on reports on experimental autoimmune orchitis. Increased numbers of different Treg phenotypes are observed in the chronically inflamed testis and in lymph nodes draining to it; however these cells are outnumbered by effector T cells. Distortion of the effector/regulatory cell balance in favour of a pro-inflammatory response is suspected to contribute to exacerbation of autoimmune disease. Under inflammatory conditions, effector T-cell subsets can overwhelm the inhibitory effect of Tregs, and pro-inflammatory cytokines may directly or indirectly affect the ability of Tregs to control autoimmunity. Therefore, Tregs alone may not be sufficient to limit excessive T-cell activation in autoimmune settings. Treg immunotherapy for autoimmune disease treatment aims to restore the normal balance of effector and Tregs in the inflamed tissue. Therapies combining the transfer of Tregs with Treg-stabilising drugs are expected to be the most effective to restrain autoimmune diseases.