IL-12 and type-I IFN synergize for IFN-γ production by CD4 T cells, while neither are required for IFN-γ production by CD8 T cells after Listeria monocytogenes infection

• Published in: The Journal of immunology (1950) 2007-04, Vol.178 (7), p.4498-4505
• Main Authors: Way, Sing Sing, Havenar-Daughton, Colin, Kolumam, Ganesh A., Orgun, Nural N., Murali-Krishna, Kaja
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

Differentiation of antigen specific T cells into IFN-γ producers is essential for protective immunity to intracellular pathogens. In addition to stimulation through the TCR and costimulatory molecules, IFN-γ production is thought to require other inflammatory cytokines. Two such inflammatory cytokines are IL-12 and type-I IFN (IFN-I), which have been shown to have a role in priming naïve T cells IFN-γ production in vitro . However, their role in priming antigen specific T cells for IFN-γ production during experimental infection in vivo is less clear. Herein, we examine the requirements for IL-12 and IFN-I, either individually or in combination, for priming antigen specific T cells for IFN-γ production after Listeria monocytogenes infection. Surprisingly, neither individual nor combined defects in IL-12 or IFN-I signaling altered IFN-γ production by antigen specific CD8 T cells after Lm infection. In contrast, individual defects in either IL-12 or IFN-I signaling conferred partial (∼50%) reductions, while combined deficiency in both IL-12 and IFN-I signaling conferred more dramatic (75−95%) reductions in IFN-γ production by antigen specific CD4 T cells after Lm infection. The additive effects of IL-12 and IFN-I signaling on IFN-γ production by CD4 T cells were further demonstrated by adoptive transfer of transgenic IFN-IR+/+ and IFN-IR−/− CD4 T cells into normal and IL-12-deficient mice, and infection with recombinant Lm. These results demonstrate an important dichotomy between the signals required for priming IFN-γ production by CD4 and CD8 T cells in response to bacterial infection.