title: CXCR3-dependent recruitment of antigen-specific T lymphocytes to the liver during murine cytomegalovirus infection.
abstract: Innate inflammatory events promoting antiviral defense in the liver against murine cytomegalovirus (MCMV) infection have been characterized. However, the mechanisms that regulate the selective recruitment of inflammatory T lymphocytes to the liver during MCMV infection have not been defined. The studies presented here demonstrate the expression of monokine induced by gamma interferon (IFN-gamma; Mig/CXCL9) and IFN-gamma-inducible protein 10 (IP-10/CXCL10) in liver leukocytes and correlate their production with the infiltration of MCMV-specific CD8 T cells into the liver. Antibody-mediated neutralization of CXCL9 and CXCL10 and studies using mice deficient in CXCR3, the primary known receptor for these chemokines, revealed that CXCR3-dependent mechanisms promote the infiltration of virus-specific CD8 T cells into the liver during acute infection with MCMV. Furthermore, CXCR3 functions augmented the hepatic accumulation of CD8 T-cell IFN-gamma responses to MCMV. Evaluation of protective functions demonstrated enhanced pathology that overlapped with transient increases in virus titers in CXCR3-deficient mice. However, ultimate viral clearance and survival were not compromised. Thus, CXCR3-mediated signals support the accumulation of MCMV-specific CD8 T cells that contribute to, but are not exclusively required for, protective responses in a virus-infected tissue site.
authors.affiliation: Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Hokeness
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Deweerd
authors.forename: Michael W
authors.initials: MW
authors.lastname: Munks
authors.forename: Casey A
authors.initials: CA
authors.lastname: Lewis
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Gladue
authors.forename: Thais P
authors.initials: TP
authors.lastname: Salazar-Mather
mesh_terms: D000818:Animals; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine