Immunity · 2015
CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells.
СтатьяResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди
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Hickman Heather D, Reynoso Glennys V, Ngudiankama Barbara F, Cush Stephanie S, Gibbs James, Bennink Jack R, Yewdell Jonathan W
Аннотация
CD8(+) 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.