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

The unique cytokine responsiveness of virtual memory T (T_VM) cells endows them with a potent capacity for bystander activation and effector function. Here, we investigated the antigen-independent impact of microbial infections on T_VM cells. While <i>Salmonella typhimurium</i> or influenza A virus had no discernible effect, infection with lymphocytic choriomeningitis virus (LCMV) resulted in a rapid and profound depletion of T_VM and true naive (T_N) cells. Unlike T_N cells, residual T_VM 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 T_VM cell numbers and enhanced TCR sensitivity observed up to 18 months post infection, coincident with an attenuation of the senescent T_VM cell phenotype. These findings reveal a previously unrecognized mechanism by which early-life pathogen exposure imprints long term changes on T_VM cells, with broad implications for immune aging and lifelong immune competence.