Open AccessTissue-resident CD8 + T cells drive age-associated chronic lung sequelae after viral pneumonia
Author(s) -
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
Publication year - 2020
Publication title -
science immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.83
H-Index - 51
ISSN - 2470-9468
DOI - 10.1126/sciimmunol.abc4557
Subject(s) - pneumonia , immunology , lung , cd8 , biology , inflammation , fibrosis , influenza a virus , respiratory system , respiratory tract , virus , medicine , immune system , pathology , anatomy
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 RM ) in the respiratory tract of aged hosts. T RM cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T RM cells 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. 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 after viral pneumonia.