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

PLoS One. 2012;7(7):e40865. doi: 10.1371/journal.pone.0040865. Epub 2012 Jul 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Immunity / immunology*
  • Infections / immunology*
  • Infections / microbiology
  • Infections / pathology
  • Infections / virology
  • Inflammation / immunology
  • Inflammation / pathology
  • Interferon Type I / immunology*
  • Interleukin-12 / immunology*
  • Listeriosis / immunology
  • Listeriosis / pathology
  • Lymphocyte Activation / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • T-Box Domain Proteins / metabolism
  • Vesiculovirus / immunology

Substances

  • Eomes protein, mouse
  • Interferon Type I
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-12