Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells

Chiara Romagnani, Mariella Della Chiesa, Siegfried Kohler, Beate Moewes, Andreas Radbruch, Lorenzo Moretta, Alessandro Moretta, Andreas Thiel

Research output: Contribution to journalArticle

Abstract

Plasmacytoid dendritic cells (pDC) represent a specialized cell population that produce type I interferon (IFN) in response to virus. Although type I IFN is a natural killer (NK) cell modulator, a direct role for pDC in coordinating NK cell functions has not yet been elucidated in detail, especially in humans. Here we report that human pDC, following engagement of Toll-like receptor (TLR) 9, not only activate autologous NK cells, as indicated by the induction of CD69 expression, but also enhance their effector functions, especially cytotoxicity. Moreover, they can induce selective proliferation of CD56bright CD16- NK cells. This activity can be strongly augmented by the addition of autologous CD4+ CD25- T helper cells in an IL-2-dependent fashion. Strikingly, CD4+ CD25hi T regulatory (Treg) cells completely abrogate this IL-2-dependent proliferation of NK cells, while they are not able to influence NK cell activation or proliferation solely induced by pDC. Our data show that TLR9-engaged pDC represent a critical stimulus for human NK cells and that CD4+ Th cells and CD4+ CD25hi Treg cells play an important role in modulating human NK cell responses.

Original languageEnglish
Pages (from-to)2452-2458
Number of pages7
JournalEuropean Journal of Immunology
Volume35
Issue number8
DOIs
Publication statusPublished - Aug 2005

Keywords

  • CD4 CD25 T regulatory cells
  • CpG
  • Natural killer cells
  • Plasmacytoid DC
  • Type I interferon

ASJC Scopus subject areas

  • Immunology

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