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

被引:128
作者
Fuchs, A
Cella, M
Kondo, T
Colonna, M
机构
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[2] Nagasaki Univ, Ctr Neurol, Dept Clin Res, Nagasaki 852, Japan
关键词
D O I
10.1182/blood-2004-12-4802
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 IPCcs after in vitro culture with interleukin 3 (IL-3). Crosslinking of NKp44 does not trigger IPC-mediated cytotoxicity but, paradoxically, inhibits interferon alpha (IFIN-alpha) production by IPCs in response to cytosine-phosphate-guanosine (CpG) oilgonucleotides. 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.
引用
收藏
页码:2076 / 2082
页数:7
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