CD4 and Sepsis: Although there are likely a number of mechanisms that are responsible for the protective effect of anti-PD-1, anti-PD-L1 and anti-CTLA-4 in sepsis, one likely mechanism is their ability to reverse the sepsis-induced suppression in IFN-γ production.All three antibodies had demonstrable efficacy in increasing either splenocyte IFN-γ production or the percentage of IFN-γ positive CD4 and/or CD8 T cells (Figures 4, 5, 6, 7).(Note that differing effects on host immunity have recently been observed in animals treated with different isotypeantibodies to CTLA-4 [40]).