Evidence for active immunological regulation in prevention of testicular autoimmune disease independent of the blood-testis barrier.
It has long been considered that autoimmune disease of the testis is prevented by sequestration of testis-specific autoantigens on germ cells behind the blood-testis (BT) barrier. However, we now have evidence that not all such antigens are sequestered. Some appear to reside on germ cells in the basal compartment of the seminiferous tubule where they are accessible to antibodies and to circulating activated T cells. Mice immunized with syngeneic testis homogenate are found to have immunoglobulin G (IgG) bound to cells in the basal compartment before onset of orchitis. This IgG is absorbed from circulation by the testis and, therefore, found only in the serum of mice orchiectomized before immunization. When the IgG is eluted from the testis, it is found to react preferentially with testicular cells enriched in preleptotene spermatocytes. T cells from mice immunized with testis can be transferred to naive syngeneic mice where they infiltrate the testis to cause orchitis. This implies that the BT barrier does not need to be breached directly for specific T cells to have access to testicular autoantigens on antigen presenting cells. Thus, active systemic and/or local immunoregulatory mechanisms must operate to prevent testicular autoimmune disease. These mechanisms may operate at the level of suppressor T cells, nonspecific suppression in the local environment of the testis, antigen presentation in the testis, or lymphocyte trafficking in the testis. These mechanisms probably operate only on the afferent limb of the immune response since they are overridden and orchitis occurs once testis-specific activated T cells are generated.
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D001814:Blood-Testis Barrier; D006801:Humans; D008297:Male; D013733:Testicular Diseases / Q000276:immunology / Q000517:prevention & control*; D013737:Testis / Q000276:immunology*
D001324:Autoantigens