Aging Compromises Terminal Differentiation Program of Cytotoxic Effector Lineage and Promotes Exhaustion in CD8⁺ T Cells Responding to Coronavirus Infection.

ABSTRACT: T cell aging increases the risk of viral infection-related morbidity and mortality and reduces vaccine efficacy in the elderly. A major hallmark of T cell aging is the loss of quiescence and shift toward terminal differentiation during homeostasis. However, how aging impacts the differentiation program of virus-specific T cells during infection is unclear. Here, in a murine coronavirus (MHV) infection model with age-associated increased mortality, we demonstrate that aging impairs, instead of promoting, the terminal differentiation program of virus-specific CD8⁺ T cells. Upon infection, CD8⁺ and CD4⁺ T cells in old mice showed marked reduction in clonal expansion and upregulation of immune checkpoints associated with T cell exhaustion. Bulk and single-cell

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC12341792 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature