The dual role of CD8 T cells in influenza control and lung pathology is increasingly appreciated. To explore whether protective and pathological functions can be linked to specific subsets, we dissected CD8 T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8 T subpopulations during peak viral load and infection-resolved state. While enrichment of a Cxcr3 CD8 T effector subset was associated with a more robust cytotoxic response, both CD8 T effector and central memory exhibited equally potent effector potential. The scRNA-seq analysis identified unique regulons regulating the cytotoxic response in CD8 T cells. The late-stage CD8 T blockade in influenza-cleared lungs or continuous CXCR3 blockade mitigated lung injury without affecting viral clearance. Furthermore, adoptive transfer of wild-type CD8 T cells exacerbated influenza lung pathology in Cxcr3 mice. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury.

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http://dx.doi.org/10.1126/sciadv.adj1120DOI Listing

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