Human memory T cells with a naïve phenotype accumulate with aging and respond to persistent viruses

The numbers of naive T cells decrease, and the susceptibility to new microbial infections increases with age. Here, we describe a new subset of phenotypically naive human CD8(+)T cells that rapidly secrete multiple cytokines in response to persistent viral antigens but differ transcriptionally from memory and effector T cells. The frequency of these CD8(+)T cells, named T memory cells with naïve phenotype (T(MNP)) increased with age and following severe acute infection and inversely correlated with the residual immune capacity to respond to new infections with age. CD8(+)T(MNP) cells represent a new potential target for immunotherapy of persistent infections, and should be accounted for and subtracted from the naive pool if truly naive T cells are needed to respond to antigens.