CXCR3 Chemokine Receptor Enables Local CD8+ T Cell Migration for the Destruction of Virus-Infected Cells

SummaryCD8+ T cells play a critical role in limiting peripheral virus replication, yet how they locate virus-infected cells within tissues is unknown. Here, we have examined the environmental signals that CD8+ T cells use to localize and eliminate virus-infected skin cells. Epicutaneous vaccinia virus (VV) infection, mimicking human smallpox vaccination, greatly increased expression of the CXCR3 chemokine receptor ligands CXCL9 and CXCL10 in VV-infected skin. Despite normal T cell numbers in the skin, Cxcr3−/− mice exhibited dramatically impaired CD8+-T-cell-dependent virus clearance. Intravital microscopy revealed that Cxcr3−/− T cells were markedly deficient in locating, engaging, and killing virus-infected cells. Further, transfer of wild-type CD8+ T cells restored viral clearance in Cxcr3−/− animals. These findings demonstrate a function for CXCR3 in enhancing the ability of tissue-localized CD8+ T cells to locate virus-infected cells and thereby exert anti-viral effector functions