The testis as an immune-privileged site allows long-term survival of allogeneic and xenogeneic transplants. Testicular Sertoli cells (SCs) can confer local immunoprotection for cotransplanted cells and may provide a means of overcoming the obstacles associated with cell transplantation. This study was to investigate the role of SCs and its association with Treg and Th17 subsets in allogeneic T cell responses in vitro. Sertoli cells were purified from testis of BalB/c mice and co-cultured with C57BL/6 mice Naïve CD4+T cells (CD4+CD62L+CD25-). Co-cultured Sertoli cells were found to strongly up-express B7-H1 and MHC class II by Western blot analysis, those contributed to attenuate T cell immune response. In addition, The mRNA expression of TGF-β1 on co-cultured Sertoli cells was increased by 3.2-fold. Importantly, the frequency of CD25+Foxp3+ T cells differentiated from Naïve CD4+T cells co-cultured with Sertoli cells was increased from <1% to 17.6% as assessed by FACS analysis. It is hypothesized that the function of Sertoli cells involved in inducing allogeneic Treg differentiation is TGF-β1 dependent. To induce Th17 differentiation, dendritic cells (DCs) were purified from bone marrow of BalB/c mice and co-cultured with C57BL/6 mice Naïve CD4+T cells (CD4+ CD25-) for 4 days in the presence of neutralizing anti-mouse TGF-β mAb. The ratio of IL-17A+ cells detected by FACS in these cocultures was 1.07%, higher than 0.14% in the culture with Naïve CD4+T cells alone. To investigate the function of Sertoli cells in regulating Th17 differentiation, Sertoli cell and CD4+CD62L+CD25- T cell co-culture supernatant, derived from Sertoli-induced Tregs, was added into the wells of DC and CD4+ CD25- T cell cocultures. Significantly, the ratio of IL-17A+ cells in the presence of Sertoli/ Naïve CD4+T cells co-culture supernatant was decreased to 0.22%, whereas Sertoli cell supernatant did not reduce the number of IL-17A+ cells (0.99%). In conclusions, in vitro Sertoli cells can induce allogeneic Treg differentiation and suppress DCs-induced allogeneic Th17 differentiation, mediated by Tregs.

CITATION INFORMATION: Xie L, Jiang W. Function of Sertoli Cells in Regulating Allogeneic T Cell Differentiation into Treg and Th17 In Vitro. Am J Transplant. 2016;16 (suppl 3).

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