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John Goulding, Georges Abboud, Vikas Tahiliani, Pritesh Desai, Tarun E Hutchinson, Shahram Salek-Ardakani, CD8 T Cells Use IFN-γ To Protect against the Lethal Effects of a Respiratory Poxvirus Infection, The Journal of Immunology, Volume 192, Issue 11, June 2014, Pages 5415–5425, https://doi.org/10.4049/jimmunol.1400256
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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.