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

Abstract

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