Tissue-resident CD8+T cells drive age-associated chronic lung sequelae following viral pneumonia

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic non-resolving lung pathology and exaggerated accumulation of CD8 + tissue-resident memory T cells (T RM ) in the respiratory tract of aged hosts. T RM accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T RM 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. Strikingly, 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 following viral pneumonia in aged hosts.