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

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• Virtual memory T (T_VM) cells possess unique cytokine responsiveness, enabling bystander activation and effector functions.
• Understanding antigen-independent effects of microbial infections on T_VM cells is crucial for immune competence.

Purpose of the Study:

• To investigate the impact of microbial infections on T_VM cell populations.
• To determine if early-life infections induce lasting changes in T_VM cell phenotype and function.

Main Methods:

• Mice were infected with specific pathogens: *Salmonella typhimurium*, influenza A virus, or lymphocytic choriomeningitis virus (LCMV).
• Flow cytometry and T cell receptor (TCR) responsiveness assays were used to analyze T_VM and true naive (T_N) cell populations post-infection.
• Longitudinal studies assessed T_VM cell changes up to 18 months post-infection, including senescence markers.

Main Results:

• LCMV infection, unlike *S. typhimurium* or influenza, caused rapid depletion of T_VM and T_N cells.
• Residual T_VM cells post-LCMV infection displayed a less differentiated phenotype and increased TCR responsiveness compared to controls.
• These alterations in T_VM cell number and function persisted into advanced age (18 months post-infection), with reduced T_VM senescence.

Conclusions:

• Early-life LCMV infection induces long-term alterations in T_VM cell populations.
• These pathogen-induced changes in T_VM cells may influence immune aging and lifelong immune competence.
• A novel mechanism of early-life pathogen exposure imprinting on T_VM cells is revealed.