Immunology

Mouse Sertoli Cells Display Phenotypical and Functional Traits of Antigen-Presenting Cells in Response to Interferon Gamma

Abstract
The testis is regarded as an immunologically privileged site because it tolerates either autoantigenic germ cells or allografts. Since the blood testis barrier represents an incomplete immunological barrier, we have explored whether Sertoli cells, the somatic cells of the seminiferous epithelium, might play active roles in immune evasion. We report data indicating that B7-H1-mediated co-inhibition, an immunomodulatory mechanism based on cell-cell interaction, can be activated in Sertoli cell-lymphocyte co-cultures. We have found that, in response to IFNG, mouse Sertoli cells strongly up-regulate the negative co-stimulatory ligand B7-H1 but remain devoid of positive co-stimulatory molecules. Blockade of B7-H1 on Sertoli cell surface resulted in enhanced proliferation of CD8⁺ T cells co-cultured with Sertoli cells. Moreover, IFNG-stimulated Sertoli cells were found to express, concurrent with B7-H1, MHC class II. We have therefore hypothesized that Sertoli cells could function as non professional tolerogenic APCs by inducing enrichment in regulatory T cells in a mixed T lymphocyte population. Interestingly, we found that co-culturing T cells with Sertoli cells can indeed induce an increase in CD4⁺CD25⁺FOXP3⁺ T regulatory cells (Treg) and a decrease in CD4⁺CD25^- T cells, suggesting Sertoli cell-mediated Treg conversion; this process was found to be B7-H1-independent. Altogether these data show that Sertoli cells are potentially capable of down-regulating the local immune response, on one hand by directly inhibiting CD8⁺ T cell proliferation through B7-H1 and, on the other hand, by inducing an increase in regulatory T cells which might suppress other bystander T cells.

Key words: Immunology • Testis • Sertoli cells • Spermatogenesis • Inflammation

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