# LCMV-mediated loss of virtual memory CD8 T cells yields a functionally enhanced T cell subset

## TL;DR

Infection with LCMV in mice leads to a lasting change in a specific type of T cells, making them more responsive and less aged over time.

## Contribution

This study reveals that LCMV infection selectively depletes and functionally enhances virtual memory CD8 T cells, with long-term effects on immune function.

## Key findings

- LCMV infection causes a rapid and profound depletion of TVM and true naive cells.
- Remaining TVM cells show heightened TCR responsiveness and a less differentiated phenotype.
- These changes persist into advanced age, with reduced TVM numbers and enhanced TCR sensitivity.

## Abstract

The unique cytokine responsiveness of virtual memory T (TVM) cells endows them with a potent capacity for bystander activation and effector function. Here, we investigated the antigen-independent impact of microbial infections on TVM cells. While Salmonella typhimurium or influenza A virus had no discernible effect, infection with lymphocytic choriomeningitis virus (LCMV) resulted in a rapid and profound depletion of TVM and true naive (TN) cells. Unlike TN cells, residual TVM cells exhibited a less differentiated phenotype and heightened T cell receptor (TCR) responsiveness, compared to cells from uninfected mice. Notably, these changes persisted into advanced age, with sustained reductions in TVM cell numbers and enhanced TCR sensitivity observed up to 18 months post infection, coincident with an attenuation of the senescent TVM cell phenotype. These findings reveal a previously unrecognized mechanism by which early-life pathogen exposure imprints long term changes on TVM cells, with broad implications for immune aging and lifelong immune competence.

•LCMV infection of mice causes a dramatic loss of TVM cells•The loss of TVM cells selectively targeted the more differentiated or regulatory cells•TVM cells remaining after infection are more responsive to TCR mediated stimulation•The loss, and coincident increase in TCR sensitivity, was maintained over the life course

LCMV infection of mice causes a dramatic loss of TVM cells

The loss of TVM cells selectively targeted the more differentiated or regulatory cells

TVM cells remaining after infection are more responsive to TCR mediated stimulation

The loss, and coincident increase in TCR sensitivity, was maintained over the life course

Immunology; components of the immune system