Antigen-specific T(H)17 cells offset the age-related decline in durable T cell immunity.

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 (T(H)17) 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 T(H)17 cells that compensate for CD8(+) T cell defects.