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CD8 T cells use IFN-? 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-?-mediated pathways in protection against virus induced morbidity and mortality. Unexpectedly, we observed that protection against death was mediated by IFN-? without any involvement of the perforin or TRAIL-dependent pathways. IFN-? 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-? 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-? 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.

SUBMITTER: Goulding J

PROVIDER: S-EPMC4036466 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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CD8 T cells use IFN-γ to protect against the lethal effects of a respiratory poxvirus infection.

Goulding John J Abboud Georges G Tahiliani Vikas V Desai Pritesh P Hutchinson Tarun E TE Salek-Ardakani Shahram S

Journal of immunology (Baltimore, Md. : 1950) 20140418 11

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. Unexpectedl ...[more]

PMID: 24748494

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CD8 T cells use IFN-? to protect against the lethal effects of a respiratory poxvirus infection.

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CD8 T cells use IFN-γ to protect against the lethal effects of a respiratory poxvirus infection.

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