CD4+ T helper cells use CD154-CD40 interactions to counteract T reg cell- mediated suppression of CD8+ T cell responses to influenza

Academic Article

Abstract

  • CD4 T cells promote CD8 T cell priming by licensing dendritic cells (DCs) via CD40-CD154 interactions. However, the initial requirement for CD40 signaling may be replaced by the direct activation of DCs by pathogen-derived signals. Nevertheless, CD40-CD154 interactions are often required for optimal CD8 T cell responses to pathogens for unknown reasons. Here we show that CD40 signaling is required to prevent the premature contraction of the influenzaspecific CD8 T cell response. CD40 is required on DCs but not on B cells or T cells, whereas CD154 is required on CD4 T cells but not CD8 T cells, NKT cells, or DCs. Paradoxically, even though CD154-expressing CD4 T cells are required for robust CD8+ T cell responses, primary CD8 T cell responses are apparently normal in the absence of CD4 T cells. We resolved this paradox by showing that the interaction of CD40-bearing DCs with CD154-expressing CD4 T cells precludes regulatory T cell (T reg cell)-mediated suppression and prevents premature contraction of the influenza-specific CD8+ T cell response. Thus, CD4 T helper cells are not required for robust CD8 T cell responses to influenza when T reg cells are absent. © 2013 Ballesteros-Tato et al. + + + + + + + + + + + +
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Ballesteros-Tato A; León B; Lund FE; Randall TD
  • Start Page

  • 1591
  • End Page

  • 1601
  • Volume

  • 210
  • Issue

  • 8