IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8 + T cells

Alice E. Denton, Peter C. Doherty, Stephen J. Turner, Nicole L. La Gruta

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

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/lL-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.

Original languageEnglish
Pages (from-to)368-375
Number of pages8
JournalEuropean Journal of Immunology
Volume37
Issue number2
DOIs
Publication statusPublished - 1 Feb 2007
Externally publishedYes

Keywords

  • CD8 T cells
  • Cytokines
  • Influenza A virus

Cite this

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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/lL-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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IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8 + T cells. / Denton, Alice E.; Doherty, Peter C.; Turner, Stephen J.; La Gruta, Nicole L.

In: European Journal of Immunology, Vol. 37, No. 2, 01.02.2007, p. 368-375.

Research output: Contribution to journalArticleResearchpeer-review

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