Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion
Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion
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DOI：
10.1182/blood-2005-04-1351
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发表时间：
2006-01-01
期刊：
影响因子：
20.3
通讯作者：
Long, EO
中科院分区：
文献类型：
--
作者：
Bryceson, YT;March, ME;Long, EO
与体外白介素2(IL-2)激活的墨水细胞相比，新鲜分离的静息自然杀伤(NK)细胞对靶细胞的裂解能力一般较低。为了研究这种差异的基础，我们检测了几种受体对人NK细胞激活的贡献。在一种重定向的、抗体依赖的细胞毒试验中，IL-2激活的NK细胞的靶细胞裂解是由许多受体触发的。相比之下，静息NK细胞的细胞毒作用仅由CD16诱导，而不受NKp46、NKG2D、2134(CD244)、dNaM-1(CD226)或CD2诱导。CD16抗体和NKp46、2B4抗体可诱导静息NK细胞内钙离子的流动。虽然NKp46不增加CD16介导的钙离子流量，但它与所有其他受体都有协同作用。2B4与其他3种受体协同作用，NKG2D和dNaM-1分别与其他2种受体协同作用，CD2仅与NKp46协同作用。静息的NK细胞被诱导分泌肿瘤坏死因子-α(TNF-α)和干扰素-γ(干扰素-γ)，并通过特定的、成对的受体组合来杀伤靶细胞。因此，静息NK细胞的自然细胞毒作用只能通过非激活受体的相互协同刺激来诱导。这些结果揭示了静止的NK细胞上受体之间的明显和特定的协同模式。
Freshly isolated, resting natural killer (NK) cells are generally less lytic against target cells than in vitro interleukin 2 (IL-2)activated INK cells. To investigate the basis for this difference, the contribution of several receptors to activation of human NK cells was examined. Target-cell lysis by IL-2-activated NK cells in a redirected, anti body-dependent cytotoxicity assay was triggered by a number of receptors. In contrast, cytotoxicity by resting NK cells was induced only by CD16, and not by NKp46, NKG2D, 2134 (CD244), DNAM-1 (CD226), or CD2. Calcium flux in resting NK cells was induced with antibodies to CD16 and, to a weaker extent, antibodies to NKp46 and 2B4. Although NKp46 did not enhance CD16-mediated calcium flux, it synergized with all other receptors. 2B4 synergized with 3 other receptors, NKG2D and DNAM-1 each synergized with 2 other receptors, and CD2 synergized with NKp46 only. Resting NK cells were induced to secrete tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma), and to kill target cells by engagement of specific, pair-wise combinations of receptors. Therefore, natural cytotoxicity by resting NK cells is induced only by mutual costimulation of nonactivating receptors. These results reveal distinct and specific patterns of synergy among receptors on resting NK cells.