# Antigen-specific TH17 cells offset the age-related decline in durable T cell immunity

## TL;DR

The study shows that TH17 cells help maintain strong immunity in older adults despite age-related decline in CD8+ T cells.

## Contribution

The novel finding is that antigen-specific TH17 cells compensate for CD8+ T cell defects in aging, enabling durable vaccine immunity.

## Key findings

- CD8+ T cells show age-related decline in memory and diversity, while TH17 CD4+ T cells are preserved.
- Adjuvanted vaccines in older adults enhance TH17 cells and prevent conversion to regulatory T cells.
- Durable immunity in aging relies on TH17 cells rather than CD8+ T cells.

## Abstract

Older adults are susceptible to infections in part due to waning of immune memory. To uncover mechanisms of a long-lasting immune memory, we contrasted varicella zoster virus antigen–specific memory T cell responses in adults vaccinated at young (<20 years) or older age (>50 years) with a live-attenuated vaccine conferring durable protection only when given at young age or with an adjuvanted component vaccine eliciting long-lasting immunity in older adults. Unlike VZV-specific CD4+ T cells, CD8+ T cells exhibited profound age-sensitive changes including memory subset shifts, reduced T cell receptor diversity, and loss of stem-like features. Vaccination of older adults with the adjuvanted vaccine did not restore CD8+ defects but selectively enhanced T helper 17 (TH17) CD4+ T cells and prevented their conversion into regulatory T cells, likely through lipid metabolic regulation. Thus, durable vaccine efficacy with aging relies on antigen-specific TH17 cells that compensate for CD8+ T cell defects.

Aging impairs the CD8+ T cell VZV vaccine response, while effective VZV vaccination functions through inducing TH17 CD4+ T cells.