Prdm1 Regulates Cytokine Expression in CD4+T Cells and Alters Islet and Skin Allograft Survivals

The objective of this study was to examine the effect of Prdm1 inhibition or overexpression on levels of CD4+T cells, and islet and skin transplantation, in mice. Mice CD4+T cells (from the spleen) were cultured, purified and enriched, and then transfected with shRNA lentiviral vector Prdm1-RNAi-GFP and overexpression lentiviral vector LV-Prdm1-puro. Murine cytokine levels were then measures. Murine islet transplantation and skin transplantation model were established, and the mice were injected with CD4+T cells transfected with lentivirus Prdm1-RNAi-GFP or LV-Prdm1-puro. Levels of IFN-γ and IL-10 were measured, and the survival times of the grafts were measured and compared. The expressions of IL-4 and IL-10 were up-regulated after overexpression of Prdm1, and the expression of IFN-γ was up-regulated in CD4+T cells after inhibition of Prdm1 (P<0.05). Overexpression of Prdm1 resulted in longer islet and skin graft survival and better graft function, while inhibition of Prdm1 shortened islet and skin graft survival. Microscopic examination showed evidence of mild rejection of islet and skin grafts in the LV-Prdm1-puro, but severe rejection in the Prdm1-RNAi group. Taken together, the results indicate that overexpression of Prdm1 can prolong graft survival and induce the formation of transplant immune tolerance via secretion of Th2 cytokines by CD4+T cells. Inhibition of Prdm1 can promote transplant rejection and shorten graft survival via secretion of Th1 cytokines.