IL‐18, but not IL‐12, is required for optimal cytokine production by influenza virus‐specific CD8+ T cells
European journal of immunology, 2007•Wiley Online Library
The potent innate cytokines IL‐12 and IL‐18 are considered to be important antigen‐
independent mediators of IFN‐γ 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 …
independent mediators of IFN‐γ 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 …
Abstract
The potent innate cytokines IL‐12 and IL‐18 are considered to be important antigen‐independent mediators of IFN‐γ 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‐γ, TNF‐α, 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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