PLoS ONE (Jan 2012)

Signal 3 cytokines as modulators of primary immune responses during infections: the interplay of type I IFN and IL-12 in CD8 T cell responses.

  • Selina Jessica Keppler,
  • Kerstin Rosenits,
  • Tamara Koegl,
  • Smiljka Vucikuja,
  • Peter Aichele

DOI
https://doi.org/10.1371/journal.pone.0040865
Journal volume & issue
Vol. 7, no. 7
p. e40865

Abstract

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Signal 3 cytokines, such as IL-12 or type I IFN, support expansion and differentiation of CD8 T cells in vivo. If and how these two signal 3 cytokines compensate each other in T cell activation during different infections is so far unknown. Using CD8 T cells lacking receptors for IL-12, type I IFN or both, we show that the expansion of CD8 T cells depends on type I IFN (LCMV infection), type I IFN and IL-12 (Listeria and vesicular stomatitis virus infection) or is largely independent of the two cytokines (vaccinia virus infection). Furthermore, we show that CD8 T cells lacking IL-12 and type I IFN signals are impaired in cytokine production and cytolytic activity in the context of VSV and Listeria infection. These effector CD8 T cells fail to express KLRG1, thereby exhibiting a memory-like phenotype which correlated with lower expression of the transcription factor T-bet and higher expression of Eomes. This indicates that the variable interplay of both signal 3 cytokines is mandatory for cell fate decision of CD8 T cells in the context of different infections. Furthermore our results demonstrate that the pathogen-induced overall inflammatory milieu and not the antigen load and/or the quality of antigen presentation critically determine the signal 3 dependence of CD8 T cells.