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

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Science Immunology  06 Nov 2020:
Vol. 5, Issue 53, eabc4557
DOI: 10.1126/sciimmunol.abc4557

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Role reversal for aged T cells

Age-related changes to the adaptive immune system are associated with impaired host response and increased morbidity and mortality after respiratory virus infection. Goplen et al. used a murine model of influenza virus infection to compare the function of lung tissue–resident memory T (TRM) cells in young and aged mice. Although TRM cells typically promote robust antiviral immunity, aged mice displayed increased accumulation of dysfunctional influenza-specific TRM cells that provided less protection against heterologous infection compared with TRM cells from young mice and facilitated pathological lung fibrosis. These results provide insight into how age and prior infection may affect T cell–mediated immunity to respiratory viruses such as influenza and SARS-CoV-2 and how these factors contribute to chronic lung pathology after viral pneumonia in older individuals.


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 (TRM) in the respiratory tract of aged hosts. TRM cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that TRM cells 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. 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 after viral pneumonia.

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