Indeed, it has been reported that both FGL2 and PD-1 are expressed on T cells, macrophages, and DCs, and that targeted deletion of fgl2 or PD-1 leads to impaired T cell activity, and these events are related to the development of autoimmune diseases [6, 31, 32] . We here also observed PD-1 expression as being enhanced on T cells (both CD4 + and CD8 + T cells). It was reasonable to propose that the expression of FGL2 may have been directly regulated by PD-1 signals. Unexpectedly, our FGL2/PD-1 dual staining showed that PD-1-positive cells in the liver, thymus, spleen and lymph nodes did not co-express FGL2, indicating that the expression of FGL2 was not directly regulated by PD-1. On the other hand, the expression of FGL2 is believed to be induced by IFN-c and TNF-a [21, 22] , while PD-1 signaling has the capacity to inhibit IFN-c and TNF-a secretion from PD-1-positive immune cells [6] . Therefore, we evaluated and compared the status of IFN-c and TNF-a in both PD-1-deficient and WT mice. Definitively, the transcription of IFN-c and TNF-a genes was rapidly enhanced post-MHV-3 infection in PD-1-deficient mice, as compared to WT controls. In particular, a higher level of IFN-c was observed in NK cells but not in CD3 + T cells of PD-1deficient liver post-MHV-3 infection, indicating that the PD-1 signal can inhibit IFN-c secretion from NK cells under such condition. Conversely, injection of a the combination of anti-IFNc and anti-TNF-a blocking mAbs was able to successfully inhibit fgl2 mRNA transcription and protein expression, resulting in reduced tissue damage and significantly protecting against MHV-3-mediated mortality in these mice. These results demonstrated that up-regulation of FGL2 in PD-1-deficient mice after MHV-3 infection was controlled, at least partially, by IFN-c and TNF-a.