CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells

Immunity. 2015 Mar 17;42(3):524-37. doi: 10.1016/j.immuni.2015.02.009. Epub 2015 Mar 10.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Movement
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / immunology
  • Female
  • Gene Expression Regulation
  • Humans
  • Keratinocytes / immunology*
  • Keratinocytes / pathology
  • Keratinocytes / virology
  • Mice, Transgenic
  • Poxviridae Infections / genetics
  • Poxviridae Infections / immunology*
  • Poxviridae Infections / pathology
  • Poxviridae Infections / virology
  • Receptors, CXCR3 / deficiency
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology*
  • Signal Transduction
  • Skin / immunology*
  • Skin / pathology
  • Skin / virology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Cytotoxic / transplantation
  • Vaccinia virus / immunology*
  • Viral Load


  • Chemokine CXCL10
  • Chemokine CXCL9
  • Cxcl10 protein, mouse
  • Cxcl9 protein, mouse
  • Cxcr3 protein, mouse
  • Receptors, CXCR3