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

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.
AuthorsJohn Goulding, Georges Abboud, Vikas Tahiliani, Pritesh Desai, Tarun E Hutchinson, Shahram Salek-Ardakani
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 11 Pg. 5415-25 (Jun 1 2014) ISSN: 1550-6606 [Electronic] United States
PMID24748494 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 by The American Association of Immunologists, Inc.
Chemical References
  • Interferon-gamma
  • Animals
  • B-Lymphocytes (immunology, pathology)
  • CD4-Positive T-Lymphocytes (immunology, pathology)
  • CD8-Positive T-Lymphocytes (immunology, pathology)
  • Interferon-gamma (genetics, immunology)
  • Lung (immunology, pathology)
  • Mice
  • Mice, Knockout
  • Respiratory Tract Diseases (genetics, immunology, pathology)
  • Vaccinia (genetics, immunology, pathology)
  • Vaccinia virus (immunology)

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