Increased antigen responsiveness of naive CD8 T cells exposed to IL-7 and IL-21 is associated with decreased CD5 expression

Academic Article

Abstract

  • Exposure of naive CD8 T cells to the synergistic combination of interleukin (IL)-7 and IL-21 enables them to respond strongly to subsequent antigen stimulation. Mechanisms underlying the increased antigen responsiveness of such cytokine-primed CD8 T cells remain unknown. In this study, we showed that a brief exposure of 24 h to IL-7 and IL-21 is sufficient enough to sensitize naive P14 T-cell receptor (TCR) transgenic CD8 T cells to respond to limiting quantities of antigen, resulting in increased proliferation, interferon-γ secretion and antigen-specific cytolytic activity. Cytokine-induced increase in TCR responsiveness occurs even in the absence of costimulatory signals. Cytokine priming upregulates the expression of the γ c chain and increases IL-2 production after antigen stimulation, thus enhancing autocrine stimulation. Notably, cytokine priming induces a rapid and profound downmodulation of CD5, implicated in the negative regulation of TCR signaling, by induction of the transcriptional repressor E47. These findings show that increased antigen responsiveness of cytokine-primed CD8 T cells results from the modulation of multiple cell-surface molecules, which influence cytokine receptor and TCR signaling. © 2010 Australasian Society for Immunology Inc.
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    Digital Object Identifier (doi)

    Author List

  • Gagnon J; Chen XL; Forand-Boulerice M; Leblanc C; Raman C; Ramanathan S; Ilangumaran S
  • Start Page

  • 451
  • End Page

  • 460
  • Volume

  • 88
  • Issue

  • 4