Structural, cellular and molecular aspects of immune privilege in the testis

Abstract

The testis presents a special immunological environment, considering its property of immune privilege that tolerates allo- and auto-antigens. Testicular immune privilege was once believed to be mainly based on the sequestration of antigens from the immune system by the blood–testis barrier in the seminiferous epithelium. Substantial evidence supports the view that the combination of physical structure, testicular cells, and cytokines controls immune responses in the testis to preserve the structural and functional integrity of testicular immune privilege. Both systemic immune tolerance and local immunosuppression help maintain the immune privilege status. Constitutive expression of anti-inflammatory factors in testicular cells is critical for local immunosuppression. However, the testis locally generates an efficient innate immune system against pathogens. Disruption of these mechanisms may lead to orchitis and impair fertility. This review article highlights the current understanding of structural, cellular, and molecular mechanisms underlying the unique immune environment of the testis, particularly its immune privilege status.

Testicular defense systems: immune privilege and innate immunity

“…Multiple mechanisms and factors, including the physical structure, the local active immunosuppressive milieu and systemic immune tolerance, coordinate to regulate the immunoprivileged state in the testis. 3,22 Testicular structure contributes to immune privilege The testis is a complex organ with a unique physical structure and a large number of cell types. The mammalian testis consists of two distinct compartments: the seminiferous tubules and the interstitial spaces between the tubules (Figure 1).…”

“…Several recently published comprehensive reviews should be consulted for more in-depth information. [2][3][4] The testis can be infected by various microbial pathogens derived from circulating blood or that ascend the genitourinary tract. To elicit an appropriate and effective local response against invading pathogens, testicular cells have to overcome immune privilege.…”

Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis

“…The anatomic portion of the BTB is composed of tight junctions between the Sertoli cells (Mital, et al, 2011;Pelletier, 2011;Li et al, 2012). These tight junctions are located near the outside edge of the seminiferous tubule, just apical of the spermatogonia.…”

Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance

“…Therefore, loss of tolerance rather than loss of sequestration is the likely cause of autoimmune Because the Sertoli cell barrier effectively blocks Abs and lymphoid cells from entering the seminiferous tubules (22)(23)(24), the barrier is presumed to also prevent MGCA from entering the interstitial space to reach the immune cells (19,(25)(26)(27). Accordingly, local antigen nonspecific mechanisms are deemed sufficient to control tissue barrier integrity and excessive testis inflammation in autoimmunity, trauma, or infection (19,25,27). However, the complete antigen sequestration paradigm itself has neither been found to develop a prolonged period of MGCA-specific tolerance due to the emergence of MGCA-specific Tregs (36).…”