CXCR3, IP-10, and Mig are required for CD4+ T cell recruitment during the DTH response to HSV-1 yet are independent of the mechanism for viral clearance.
Sensitized CD4+ T cells play an essential role in delayed type hypersensitivity (DTH) elicited by HSV-1 antigen. As activated CD4+ T cells express CXCR3, we investigated whether this chemokine receptor was involved in their recruitment. Antibody blockade of CXCR3 suppressed DTH, whereas ear pinna swelling was not impaired in mice lacking the gene for CCR5, another frequently expressed chemokine receptor. CXCR3 ligands IP-10 and Mig were elevated at the DTH site. Their neutralization significantly reduced DTH ear swelling and CD4+ T cell influx. Furthermore, CXCR3 ligand expression was abrogated and DTH diminished in mice unable to make IFN-gamma, a potent inducer of IP-10 and Mig. Interestingly, neutralization of CXCR3 or its ligands did not compromise host resistance to virus replication. Collectively, these results suggest that in the sensitized host, CXCR3, IP-10, and Mig are required for optimal DTH responsiveness but are not essential for containing HSV-1 replication in the ear pinna.
Molesworth-Kenyon
Sara
S
Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36607, USA.
Mates
Aaron
A
Yin
Rong
R
Strieter
Robert
R
Oakes
John
J
Lausch
Robert
R
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000502:physiology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000502:physiology*
D000914:Antibodies, Viral; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; D007074:Immunoglobulin G; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma