Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 2, Pages 368-375Publisher
WILEY
DOI: 10.1002/eji.200636766
Keywords
CD8(+) T cells; cytokines; influenza A virus
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Funding
- NIAID NIH HHS [AI29579, AI 350395] Funding Source: Medline
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The potent innate cytokines IL-12 and IL-18 are considered to be important antigen-independent mediators of IFN-gamma production by NK cells and T lymphocytes. The present analysis addresses the physiological role of IL-12 and IL-18 in the generation of virus-specific CD8(+) T cells. Both wt C57BL/6J (B6) mice and mice with disrupted IL-12p40 (IL-12p40(-/-)) or IL-18 (IL-18(-/-)) genes were infected with an influenza A virus and the characteristics of the resultant epitope-specific CD8(+) T cell responses were compared. While IL-12 appeared to have no notable effect on either virus growth or on CD8(+) T cell response profiles, the absence of IL-18 was associated with delayed virus clearance from the lung and, despite normal numbers, a significantly reduced production of IFN-gamma, TNF-alpha, and IL-2 by epitope-specific CD8(+) T cells. While this cytokine phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no evidence was seen for any additive effect. Together, our results suggest that IL-18, but not IL-12, induces optimal, antigen-specific production of key cytokines by CD8(+) T cells for the efficient clearance of influenza virus from the lungs of infected mice.
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