Tissue-resident CD8 T cells drive age-associated chronic lung sequelae after viral pneumonia.

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) in the respiratory tract of aged hosts. T cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8 T cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.