Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells
Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells
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DOI：
10.1158/1078-0432.ccr-05-2306
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发表时间：
2006-04-01
影响因子：
11.5
通讯作者：
Teruel, A
中科院分区：
文献类型：
--
作者：
Jewett, A;Cacalano, NA;Teruel, A
在口腔癌患者中观察到CD16 （Fc γ RIII）受体下调和自然杀伤（NK）细胞功能丧失。然而，CD16受体减少的机制和意义都没有得到充分的了解。针对CD16表面受体的抗体可负调控NK细胞的细胞毒活性和存活。将抗cd94抗体与F(ab)2片段或完整的抗cd16抗体联合加入NK细胞，可显著抑制NK细胞的细胞毒功能，诱导静息外周血NK细胞凋亡。在抗cd16和/或抗cd94抗体处理的NK细胞中添加白细胞介素-2可显著抑制NK细胞凋亡，提高NK细胞的功能。无论是单独使用抗cd16抗体还是联合使用抗cd94抗体，NK细胞的肿瘤坏死因子- α (tnf - α)分泌均显著增加，但ifn - γ分泌未见增加。因此，抗tnf - α抗体的加入部分抑制了抗cd94和抗cd16抗体联合介导的NK细胞凋亡。NK细胞凋亡死亡的增加也与2型炎症细胞因子的增加和趋化因子的诱导相关。因此，我们得出结论，抗体与CD16和CD94 NK细胞受体结合可诱导NK细胞死亡并发出释放趋化因子的信号。
Down-modulation of CD16 (Fc gamma RIII) receptors and loss of natural killer (NK) cell function have been observed in oral cancer patients. However, neither the mechanisms nor the significance of the decrease in CD16 receptors have been fully understood. The cytotoxic activity and survival of NK cells are negatively regulated by antibodies directed against CD16 surface receptor. The addition of anti-CD94 antibody in combination with either F(ab)2 fragment or intact anti-CD16 antibody to NK cells resulted in significant inhibition of NK cell cytotoxic function and induction of apoptosis in resting human peripheral blood NK cells. Addition of interleukin-2 to anti-CD16 and/or anti-CD94 antibody-treated NK cells significantly inhibited apoptosis and increased the function of NK cells. There was a significant increase in tumor necrosis factor-alpha (TNF-alpha) but not IFN-gamma secretion in NK cells treated either with anti-CD16 antibody alone or in combination with anti-CD94 antibodies. Consequently, the addition of anti-TNF-alpha antibody partially inhibited apoptosis of NK cells mediated by the combination of anti-CD94 and anti-CD16 antibodies. Increase in apoptotic death of NK cells also correlated with an increase in type 2 inflammatory cytokines and in the induction of chemokines. Thus, we conclude that binding of antibodies to CD16 and CD94 NK cell receptors induces death of the NK cells and signals for the release of chemokines.