Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44

Blood. 2005 Sep 15;106(6):2076-82. doi: 10.1182/blood-2004-12-4802. Epub 2005 Jun 7.

Abstract

Natural killer (NK) cell-mediated cytotoxicity is triggered by multiple activating receptors associated with the signaling adaptor protein DNAX activation protein 12/killer cell-activating receptor-associated protein (DAP12/KARAP). Here, we show that one of these receptors, NKp44, is present on a subset of natural interferon-producing cells (IPCs) in tonsils. NKp44 expression can also be induced on blood IPCs after in vitro culture with interleukin 3 (IL-3). Crosslinking of NKp44 does not trigger IPC-mediated cytotoxicity but, paradoxically, inhibits interferon alpha (IFN-alpha) production by IPCs in response to cytosine-phosphate-guanosine (CpG) oligonucleotides. We find that IPCs in tonsils are in close contact with CD8+ T cells and demonstrate that a subset of memory CD8+ T cells produces IL-3. Therefore, IL-3-mediated induction of NKp44 on IPCs may be an important component of the ongoing crosstalk between the innate and adaptive immune response that allows memory CD8+ T cells to control the IPC response to virus.

MeSH terms

  • CD8-Positive T-Lymphocytes / metabolism
  • Cytotoxicity, Immunologic
  • Humans
  • Immunity, Cellular / physiology
  • Immunity, Innate / physiology
  • Interferon-alpha / antagonists & inhibitors*
  • Interleukin-3 / metabolism
  • Interleukin-3 / pharmacology
  • Killer Cells, Natural / immunology*
  • Natural Cytotoxicity Triggering Receptor 2
  • Palatine Tonsil / cytology
  • Paracrine Communication / immunology
  • Receptors, Immunologic / physiology*

Substances

  • Interferon-alpha
  • Interleukin-3
  • NCR2 protein, human
  • Natural Cytotoxicity Triggering Receptor 2
  • Receptors, Immunologic