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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2076-2082.
Prepublished online as a Blood First Edition Paper on June 7, 2005; DOI 10.1182/blood-2004-12-4802.
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IMMUNOBIOLOGY
Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44
Anja Fuchs,
Marina Cella,
Takayuki Kondo, and
Marco Colonna
From the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO; and the Department of Clinical Research, Nagasaki Medical Center of Neurology, Nagasaki, Japan.
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  (IFN-) 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. (Blood. 2005;106: 2076-2082)
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