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

Nick P. Goplen, Yue Wu, Young Min Son, Chaofan Li, Zheng Wang, In Su Cheon, Li Jiang, Bibo Zhu, Katayoun Ayasoufi, Eduardo N. Chini, Aaron J. Johnson, Robert Vassallo, Andrew H. Limper, Nu Zhang, Jie Sun

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 (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.

Original languageEnglish (US)
Article numbereabc4557
JournalScience Immunology
Volume5
Issue number53
DOIs
StatePublished - Nov 6 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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