title: CD8 T cells use IFN-γ to protect against the lethal effects of a respiratory poxvirus infection.
abstract: CD8 T cells are a key component of immunity to many viral infections. They achieve this through using an array of effector mechanisms, but precisely which component/s are required for protection against a respiratory orthopox virus infection remains unclear. Using a model of respiratory vaccinia virus infection in mice, we could specifically determine the relative contribution of perforin, TRAIL, and IFN-γ-mediated pathways in protection against virus induced morbidity and mortality. Unexpectedly, we observed that protection against death was mediated by IFN-γ without any involvement of the perforin or TRAIL-dependent pathways. IFN-γ mRNA and protein levels in the lung peaked between days 3 and 6 postinfection. This enhanced response coincided with the emergence of virus-specific CD8 T cells in the lung and the cessation of weight loss. Transfer experiments indicated that CD8 T cell-autonomous expression of IFN-γ restricts virus-induced lung pathology and dissemination to visceral tissues and is necessary for clearance of virus. Most significantly, we show that CD8 T cell-derived IFN-γ is sufficient to protect mice in the absence of CD4 and B-lymphocytes. Thus, our findings reveal a previously unappreciated mechanism by which effector CD8 T cells afford protection against a highly virulent respiratory orthopox virus infection.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610.
authors.forename: John
authors.initials: J
authors.lastname: Goulding
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610.
authors.forename: Georges
authors.initials: G
authors.lastname: Abboud
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610.
authors.forename: Vikas
authors.initials: V
authors.lastname: Tahiliani
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610.
authors.forename: Pritesh
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610.
authors.forename: Tarun E
authors.initials: TE
authors.lastname: Hutchinson
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610 ssalek@ufl.edu.
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012140:Respiratory Tract Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014615:Vaccinia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D007371:Interferon-gamma
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