Virology

Immune system

Effector

Interleukin 21

Gene

Antigen

Biology

Phenotype

Cytotoxic T cell

In vitro

Immunology

Genetics

Nature Immunology

Nikolich-Žugich and colleagues describe a unique subset of human T cells with a naive phenotype and the ability to rapidly produce cytokines in response to engagement of the T cell antigen receptor. The number of naive T cells decreases and susceptibility to new microbial infections increases with age. Here we describe a previously unknown subset of phenotypically naive human CD8+ T cells that rapidly secreted multiple cytokines in response to persistent viral antigens but differed transcriptionally from memory and effector T cells. The frequency of these CD8+ T cells, called 'memory T cells with a naive phenotype' (TMNP cells), increased with age and after severe acute infection and inversely correlated with the residual capacity of the immune system to respond to new infections with age. CD8+ TMNP cells represent a potential new target for the 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.

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