The PD-1 pathway regulates development and function of memory CD8+ T cells following respiratory viral infection

The PD-1:PD-L co-inhibitory pathway regulates dysfunctional T cells in chronic viral infection and cancer, but the role of this pathway in effector and memory responses following acute infection or vaccination remains less clear. Here we demonstrated that in the absence of signals from the PD-1 pathway, cell intrinsic alterations during initial CD8+ T cell priming resulted in excessive early CD8+ T cell expansion, but increased CD8+ T cell contraction and aberrant effector to memory CD8+ T cell transition. Overall, our studies revealed a critical and previously unappreciated role for PD-1 as an integrator of early CD8+ T cell activation signals that promoted optimal CD8+ T cell memory formation and durability. This novel PD-1 function has therapeutic implications for the generation of T cell memory during PD-1 cancer immunotherapy and modulation of the PD-1 pathway to enhance immune memory following acute infection or prophylactic vaccination.

12

Pauken KE, Godec J, Odorizzi PM, Brown KE, Yates KB, Ngiow SF, Burke KP, Maleri S, Grande SM, Francisco LM, Ali MA, Imam S, Freeman GJ, Haining WN, Wherry EJ, Sharpe AH