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

Eur J Immunol. 2007 Feb;37(2):368-75. doi: 10.1002/eji.200636766.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology*
  • Cytokines / biosynthesis*
  • Influenza A virus / immunology*
  • Interleukin-12 / metabolism*
  • Interleukin-18 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Antigen, T-Cell / immunology


  • Cytokines
  • Interleukin-18
  • Receptors, Antigen, T-Cell
  • Interleukin-12