CD160-Associated CD8 T-Cell Functional Impairment Is Independent of PD-1 Expression

Expression of co-inhibitory molecules is generally associated with t-cell dysfunction in chronic viral infections such as hiv or hcv. however,their relative contribution in the t-cell impairment remains unclear. in the present study,we have evaluated the impact of the expression of co-inhibitory molecules such as 2b4,pd-1 and cd160 on the functions of cd8 t-cells specific to influenza,ebv and cmv. we show that cd8 t-cell populations expressing cd160,but not pd-1,had reduced proliferation capacity and perforin expression,thus indicating that the functional impairment in cd160+ cd8 t cells may be independent of pd-1 expression. the blockade of cd160/cd160-ligand interaction restored cd8 t-cell proliferation capacity,and the extent of restoration directly correlated with the ex vivo proportion of cd160+ cd8 t cells suggesting that cd160 negatively regulates tcr-mediated signaling. furthermore,cd160 expression was not up-regulated upon t-cell activation or proliferation as compared to pd-1. taken together,these results provide evidence that cd160-associated cd8 t-cell functional impairment is independent of pd-1 expression. © 2014 viganò et al.