Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44.
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.
Fuchs
Anja
A
Department of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110, USA.
Cella
Marina
M
Kondo
Takayuki
T
Colonna
Marco
M
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D016898:Interferon-alpha / Q000037:antagonists & inhibitors*; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D055629:Natural Cytotoxicity Triggering Receptor 2; D014066:Palatine Tonsil / Q000166:cytology; D019899:Paracrine Communication / Q000276:immunology; D011971:Receptors, Immunologic / Q000502:physiology*
D016898:Interferon-alpha; D007377:Interleukin-3; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D011971:Receptors, Immunologic