Work

CD8+ T cell transcriptional reprogramming toward TCF7-low cytotoxicity drives immune aging in viral ARDS

Year: 2026

Type: article

Abstract: Viral acute respiratory distress syndrome (ARDS) exhibits distinct clinical outcomes across age groups, but the immune mechanisms underlying this disparity remain unclear. Here, we integrated single-cell transcriptomic profiling, T cell receptor repertoire analysis, serum proteomics, and functional validation to characterize age-dependent T cell remodeling in influenza-associated ARDS. Adult ARDS was characterized by reduced T cell receptor diversity, expansion of CD8 + effector memory T cells, and enhanced cytotoxic programs marked by increased granzyme B (GZMB) expression compared with pediatric ARDS. At the transcriptional level, adult CD8 + effector memory T cells displayed a TCF7-low state associated with activation of a TGFB1-related RUNX3/PRDM1 program. In vitro experiments further demonstrated that TGFB1 promoted cytotoxic programming in CD8 + effector memory T cells and increased epithelial injury in a co-culture model. These findings identify age-associated CD8 + T cell remodeling as a potential mechanism contributing to immune dysregulation in viral ARDS.

Source: iScience

DOI: 10.1016/j.isci.2026.117774