To determine whether FGL2-mediated PCA activity was also involved in inducing damage in the other organs of PD-1-deficient mice, the expression of FGL2 was analyzed in the thymus, spleen and lymph nodes. Immunohistochemistry evidenced that FGL2positive cells were also present in these organs. In thymus and lymph nodes, FGL2-positive cells were detected in both the medulla and cortex. In spleen, however, the positive cells were only found in the red pulp. Again, the expression of FGL2 appeared to be restricted to the cell membrane and cytoplasma. The distribution of FGL2-positive cells in PD-1-deficient mice had not changed after 72 h of MHV-3 infection, but the number of positive cells in the examined organs was enhanced significantly and the levels of expression were much stronger (Fig. 5A ). In addition, the transcription of fgl2 in the spleen of PD-1-deficient mice was also significantly increased in response to infection (Fig. 5B) . Meanwhile, higher levels of fibrinogen deposition were found in the spleen and lymph node tissues of PD-1-deficient mice (Fig. 5C) . Moreover, the level of FGL2 present in serum, as measured by ELISA, was found to increase rapidly after infection, and the level in PD-1-deficient mice was significantly higher than that in WT littermates (Fig. 5D ). To clarify the source of FGL2, fluorescent dual staining was performed on spleen tissues and results demonstrated that FGL2 was principally associated with CD11c-positive dendritic cells (DCs), CD68-positive macrophages and CD31-positive endothelial cells (Fig. 5E ). All of these results indicated that the absence of PD-1 signaling can result in enhanced FGL2 expression, consequently inducing stronger fibrinogen deposition and more severe tissue necrosis in PD-1deficient mice following MHV-3 infection.