Autoimmune orchitis and autoimmune oophoritis

Abstract

Experimental studies predict a frequent occurrence of human gonadal autoimmunity. In spontaneous multi-organ models of autoimmune diseases, the testis and ovary are frequent targets. Although progress in clinical research has been slow, in part explained by the success of assisted reproduction techniques, experimental studies have yielded exceptional information on the fundamental mechanisms of tolerance and autoimmunity. They include the discovery and functional analysis of the CD4+ CD25+ Foxp3+ regulatory T cells (Treg) as a major tolerance mechanism, the sequel of autoimmune regulator (AIRE) gene deficiency, molecular mimicry as a basis of autoreactive T cell response, the epitope spreading phenomenon in autoantibody production, and neonatal propensity in autoimmunity development. In addition, they provide guidelines for translational research into human disease, and better understanding of chronic inflammatory conditions of the gonads associated with subfertility and infertility. Finally, knowledge of the local immune regulation in testis as an immune privilege site, and the recently discovered systemic tolerance mechanism, have contributed to a more complete understanding of the immunological control against gonadal autoantigens, as well as to the numerous human cancer antigens that they share with normal germ cell antigens in testes and ovaries (the cancer/testis antigens). In this chapter, we will present the experimental autoimmune models, followed by a description of existing data supporting an autoimmune basis in human testicular and ovarian diseases.