title: IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Alice E
authors.initials: AE
authors.lastname: Denton
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis*; D009980:Influenza A virus / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D016207:Cytokines; D020382:Interleukin-18; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12