title: CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells.
abstract: 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.
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: hhickman@mail.nih.gov.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Hickman
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Glennys V
authors.initials: GV
authors.lastname: Reynoso
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Ngudiankama
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Cush
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: James
authors.initials: J
authors.lastname: Gibbs
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Bennink
authors.affiliation: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008822:Mice, Transgenic; D011213:Poxviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D014616:Vaccinia virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3