Decreased percentages of regulatory T cells are necessary to activate Th1-Th17-Th22 responses during acute rejection of the peripheral nerve xenotransplantation in mice.

ABSTRACT

BACKGROUND: T cells have major functions in the initiation and perpetuation of nerve graft rejection. Our study aimed to investigate the function of regulatory T cells (Treg)-Th1-Th17-Th22 cells in the rejection of peripheral nerve xenotransplantation. METHODS: Adult male C57 BL/6 mice were used as the recipient for nerve xenotransplantation, and Sprague-Dawley rats were used as the donor. These nerve xenotransplanted mice were used as the experimental groups, and those that received autograft transplant were chosen as the control group. All of the animals were pretreated with interferon (IFN)-γ, interleukin (IL)-17, and IL-22 before the experiment was conducted. The percentages of spleen Treg-Th1-Th17-Th22 cells were evaluated by flow cytometry 1, 3, 7, 14, and 28 days after transplantation. Serum levels of IFN-γ, IL-17, and IL-22 were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed by Wilcoxon rank sum and Spearman correlation test. RESULTS: During acute rejection, the percentages of Th1-Th17-Th22 cells in the spleen and serum IFN-γ, IL-17, and IL-22 levels in the experimental group increased compared with those in the control group. By contrast, CD4CD25Foxp3 T cell level decreased. The rejection of xenograft was significantly prevented after the mice were treated with IL-17-neutralizing, IL-22-neutralizing, and IFN-γ-neutralizing antibodies. Moreover, the percentage of CD4CD25Foxp3 Treg was negatively correlated with the percentages of Th1-Th17-Th22 cells and levels of IL-17, IL-22, and IFN-γ. CONCLUSION: These results suggested that the Treg-Th1-Th17-Th22 cells involved in xenotransplant rejection and imbalance between Tregs and Th1-Th17-Th22 cells contribute to the acute rejection of peripheral nerve xenotransplant.