Tissue-resident CD8<SUP>+</SUP> T cells drive age-associated chronic lung sequelae after viral pneumonia

Abstract

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8(+) tissue-resident memory T cells (T-RM) in the respiratory tract of aged hosts. T-RM cell accumulation relies on elevated TGF-beta present in aged tissues. Further, we show that T-RM cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T-RM cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8(+) T-RM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T-RM cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.