Testisimmune privilege - Assumptions versus facts

Abstract

The testis has long enjoyed a reputation as an immunologically privileged site based on its ability to protect auto-antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo- or xeno-grafts. Exploration of the role of anatomical, physiological, immunological and cellular components in testis immune privilege revealed that the tolerogenic environment of the testis is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells, and resident macrophages). The blood-testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation. Testicular immune privilege is not permanent, as an effective immune response can be mounted against transplanted tissue, and bacterial/viral infections in the testis can be effectively eliminated. Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immune privilege.

Keywords: immune privilege; testis; transplantation.

Figure 1

Testis histology and schematic diagram showing the BTB present between adjacent SC. A) Testes were collected from BALB/c mice (6–8 weeks old), paraffin embedded and sectioned. Tissue section was immunostained for Wilm’s tumor 1 to detect SC nuclei (brown color, A). Section was counterstained with hematoxylin to detect cell nuclei (blue color, A). B) BTB localization and cellular components present in the testicular interstitium and seminiferous tubules. Testis interstitium consists of Leydig cells, macrophages, dendritic cells, lymphocytes (mainly T cells), lymphatics and blood vessels. Peritubular myoid cells surround the seminiferous epithelium and form a primary barrier to substances penetrating from the interstitium to the seminiferous epithelium. The more effective and complete barrier is located within the seminiferous tubules and includes the body of SC and tight junctions between adjacent SC (BTB). The BTB delimits a basal compartment in the germinal epithelium containing the spermatogonia and early preleptotene spermatocytes, and an adluminal compartment containing the spermatocytes and spermatids. sc, Sertoli cell; m, myoid cell; sg, spermatogonia; sp, spermatocyte; r, round spermatid; el, elongated spermatid; sz, spermatozoa; L, Leydig cells; BV, blood vessel; LV, lymphatic vessel.

Figure 2

Immune environment in the testis. A) Testis under normal circumstances. The seminiferous tubules (ST) with intact germ cells and interstitium with the Leydig cells (jade), macrophages and dentritic cells (purple), depicts a balanced state in the testis. B) Type 2 immune response in the testis. In the case of a bacterial/viral infection or a transplant in the testis which does not disrupt normal testicular function, a type 2 immune response is initiated. In this type of response, most of the cells in the testis secrete immunoregulatory factors (green bolts) which favor the presence of regulatory T cells and the testis maintains a milieu supporting germ cell and transplant survival. C) Type 1 immune response in the testis. Rarely, when the bacterial/viral infections or transplanted tissue outbalance the normal environment of the testis, a type 1 immune response can be initiated that results in the secretion of inflammatory factors by the different cells in the testis (red bolts), resulting in the recruitment of cytotoxic T cells. This further increases inflammation in the testis which leads to a disruption of the BTB/SC tight junctions, binding of antibody (inverted Y) within the ST and eventually a loss of germ cell populations via apoptosis.