CXCR4 controls movement and degranulation of CD8+ T cells in the influenza-infected lung via differential effects on interaction and tissue scanning
bioRxiv (Cold Spring Harbor Laboratory)(2022)
Abstract
Effector CD8+ T cell interactions are critical in controlling viral infection by directly killing infected cells but overabundant or sustained activation also exacerbates tissue damage. Chemokines promote the trafficking of effector CD8+ T cells into infected tissues, but we know little about how chemokines regulate the function of CD8+ T cells within tissues. Using a murine model of influenza A virus infection, we found that expression of the chemokine receptor CXCR4 by lung-infiltrating cytotoxic T cells correlated with the expression of the degranulation marker CD107a. Inhibition of CXCR4 reduced activation, adhesion, and degranulation of cytotoxic T cells in vitro and in vivo . Moreover, in live influenza-infected lung tissue, T cells stopped moving in lung regions with high levels of influenza antigen, and CXCR4 was essential for CD8+ T cells to execute this arrest signal fully. In contrast, CXCR4 increased the motility of CD8+ T cells in low-influenza areas of the lung. We also found that CXCR4 stimulated the effector function of lung-infiltrating cytotoxic T cells even after clearance of influenza virus, and inhibition of CXCR4 expedited the recovery of influenza-infected mice, despite delayed clearance of the replication-competent virus. Our results suggest that CXCR4 promotes the interaction strength of cytotoxic T cells in lung tissue through combined effects on T cell movement and interaction with virally infected target cells in influenza infected-lungs.
### Competing Interest Statement
The authors have declared no competing interest.
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Key words
cells,cd8<sup>+</sup>t,lung,influenza-infected
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