tetano
Editor, Senior Moderator
Sci Immunol
. 2020 Nov 6;5(53):eabc4557.
doi: 10.1126/sciimmunol.abc4557.
Tissue-resident CD8 [SUP]+[/SUP] T cells drive age-associated chronic lung sequelae after viral pneumonia
Nick P Goplen[SUP] 1 2 [/SUP], Yue Wu[SUP] 3 [/SUP], Young Min Son[SUP] 1 [/SUP], Chaofan Li[SUP] 1 [/SUP], Zheng Wang[SUP] 1 [/SUP], In Su Cheon[SUP] 1 [/SUP], Li Jiang[SUP] 1 [/SUP], Bibo Zhu[SUP] 1 [/SUP], Katayoun Ayasoufi[SUP] 3 [/SUP], Eduardo N Chini[SUP] 2 4 [/SUP], Aaron J Johnson[SUP] 3 [/SUP], Robert Vassallo[SUP] 1 [/SUP], Andrew H Limper[SUP] 1 [/SUP], Nu Zhang[SUP] 5 [/SUP], Jie Sun[SUP] 6 2 3 [/SUP]
Affiliations
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[SUP]+[/SUP] tissue-resident memory T cells (T[SUB]RM[/SUB]) in the respiratory tract of aged hosts. T[SUB]RM[/SUB] cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T[SUB]RM[/SUB] cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T[SUB]RM[/SUB] cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8[SUP]+[/SUP] T[SUB]RM[/SUB] cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T[SUB]RM[/SUB] cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.
. 2020 Nov 6;5(53):eabc4557.
doi: 10.1126/sciimmunol.abc4557.
Tissue-resident CD8 [SUP]+[/SUP] T cells drive age-associated chronic lung sequelae after viral pneumonia
Nick P Goplen[SUP] 1 2 [/SUP], Yue Wu[SUP] 3 [/SUP], Young Min Son[SUP] 1 [/SUP], Chaofan Li[SUP] 1 [/SUP], Zheng Wang[SUP] 1 [/SUP], In Su Cheon[SUP] 1 [/SUP], Li Jiang[SUP] 1 [/SUP], Bibo Zhu[SUP] 1 [/SUP], Katayoun Ayasoufi[SUP] 3 [/SUP], Eduardo N Chini[SUP] 2 4 [/SUP], Aaron J Johnson[SUP] 3 [/SUP], Robert Vassallo[SUP] 1 [/SUP], Andrew H Limper[SUP] 1 [/SUP], Nu Zhang[SUP] 5 [/SUP], Jie Sun[SUP] 6 2 3 [/SUP]
Affiliations
- PMID: 33158975
- DOI: 10.1126/sciimmunol.abc4557
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[SUP]+[/SUP] tissue-resident memory T cells (T[SUB]RM[/SUB]) in the respiratory tract of aged hosts. T[SUB]RM[/SUB] cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T[SUB]RM[/SUB] cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T[SUB]RM[/SUB] cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8[SUP]+[/SUP] T[SUB]RM[/SUB] cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T[SUB]RM[/SUB] cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.