Overexpression of programmed death-1 ligand-1 on NIT cells lead to negative regulation of allogeneic lymphocyte activation

PD-L1 have been identified as the ligand for PD-1, and shown to play a role in the regulation of immune responses. In the present study, we investigated whether overexpressing PD-L1 on islet beta cells could induce negative regulation in primary and primed allogeneic lymphocyte response. pPD-L1-EGFP or pEGFPn1 were transfected in NIT-1 cells, for establishment of pPD-L1-EGFP or pEGFPn1 stable transfectants, namely NIT-PD-L1 and NIT-EGFP. In mixed cells reaction, as compared with the controls of NIT-1 or NIT-EGFP, NIT-PD-L1-primed splenocytes showed the lowest proliferative response but severe apoptosis when restimulated with NIT-PD-L1 cells in vitro. Overexpressing PD-L1 on NIT-1 cells could downregulate IFN-gamma but upregulate IL-4 and IL-10 production by the primed lymphocytes. In addition, proliferative response of primary reactive lymphocytes stimulated with NIT-PD-L1 was lower than those lymphocytes restimulated with NIT-1 cells or NIT-EGFP cells. Our data demonstrated that PD-L1 has down-regulative effects on alloimmune responses.