Disregulated influenza A virus-specific CD8 + T cell homeostasis in the absence of IFN-γ signaling

Stephen J. Turner, Elvia Olivas, Astrid Gutierrez, Gabriela Diaz, Peter C. Doherty

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35 Citations (Scopus)

Abstract

Recent studies indicate that IFN-γ may influence both the expansion and the trafficking of virus-specific CD8 + CTL, though the effects are not necessarily consistent for different models of viral and bacterial disease. Influenza A virus infection of mice deficient for IFN-γ (IFN-γ -/- ) or deficient for the IFN-γ receptor 1 (IFNGR1 -/- ) was, when compared with the wild-type (WT) B6 controls, associated with increased Ag-specific CD8 + T cell counts in the spleen and mediastinal lymph nodes. At the same time, fewer of these CTL effectors were found in the bronchoalveolar lavage population recovered from the IFN-γ -/- mice. Comparable effects were observed for WT mice treated with a neutralizing IFN-γ-specific mAb. Transfer of WT memory Thy1.1 + CD8 + populations into Thy1.2 + B6 IFN-γ -/- or IFNGR1 -/- mice followed by intranasal virus challenge demonstrated both that IFN-γ produced by the host was important for the regulation of Ag-specific CTL numbers and that IFN-γ was likely to act directly on the T cells themselves. In addition, the prevalence of CTLs undergoing apoptosis in spleen was lower when measured directly ex vivo for IFN-γ -/- vs WT B6 mice. The present analysis is the first comprehensive demonstration that IFN-γ signaling can differentially regulate both Ag-specific CTL homeostasis in secondary lymphoid organs and trafficking to a site of virus-induced pathology.

Original languageEnglish
Pages (from-to)7616-7622
Number of pages7
JournalJournal of Immunology
Volume178
Issue number12
Publication statusPublished - 15 Jun 2007
Externally publishedYes

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