Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells.
Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells.
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DOI：
10.18632/oncotarget.17498
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发表时间：
2017-07-11
期刊：
影响因子：
--
通讯作者：
Shimizu Y
中科院分区：
文献类型：
--
作者：
Domae E;Hirai Y;Ikeo T;Goda S;Shimizu Y
Vγ 9VS 2 T细胞是人外周血γδ T细胞的主要亚群，通过识别磷酸化抗原对微生物感染和应激细胞作出应答。与抗原介导的活化机制的知识不断增长相反，Vγ 9VS 2 T细胞的抗原非依赖性和马槟榔碱介导的活化机制知之甚少。在这里，我们显示白细胞介素（IL）-12和IL-18协同激活人离体扩增的Vγ 9VS 2 T细胞。用IL-12和IL-18处理的Vγ 9 V δ2 T细胞增强效应器功能，包括IFN-γ和颗粒酶B的表达以及细胞毒性。IL-12和IL-18处理后这些增强的效应器应答与同型聚集、ICAM-1表达增强和共抑制受体B-和T-淋巴细胞衰减因子（BTLA）表达降低相关。IL-12和IL-18也诱导Vγ 9VS 2 T细胞的抗原非依赖性增殖。IL-12和IL-18刺激后IκB β、IL-12 R β2和IL-18 R α的表达增加导致STAT 4和NF-κB的持续活化。IFN-γ的产生和细胞毒性活性的增强对于使用Vγ 9VS 2 T细胞的癌症免疫疗法是至关重要的。因此，用IL-12和IL-18联合处理离体扩增的Vγ 9VS 2 T细胞可以作为治疗性活化这些细胞的新策略。
Vγ9Vδ2 T cells, the major subset of the human peripheral blood γδ T-cell, respond to microbial infection and stressed cells through the recognition of phosphoantigens. In contrast to the growing knowledge of antigen-mediated activation mechanisms, the antigen-independent and cytokine-mediated activation mechanisms of Vγ9Vδ2 T cells are poorly understood. Here, we show that interleukin (IL) -12 and IL-18 synergize to activate human ex vivo-expanded Vγ9Vδ2 T cells. Vγ9Vδ2 T cells treated with IL-12 and IL-18 enhanced effector functions, including the expression of IFN-γ and granzyme B, and cytotoxicity. These enhanced effector responses following IL-12 and IL-18 treatment were associated with homotypic aggregation, enhanced expression of ICAM-1 and decreased expression of the B- and T-lymphocyte attenuator (BTLA), a co-inhibitory receptor. IL-12 and IL-18 also induced the antigen-independent proliferation of Vγ9Vδ2 T cells. Increased expression of IκBζ, IL-12Rβ2 and IL-18Rα following IL-12 and IL-18 stimulation resulted in sustained activation of STAT4 and NF-κB. The enhanced production of IFN-γ and cytotoxic activity are critical for cancer immunotherapy using Vγ9Vδ2 T cells. Thus, the combined treatment of ex vivo-expanded Vγ9Vδ2 T cells with IL-12 and IL-18 may serve as a new strategy for the therapeutic activation of these cells.
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影响因子：
15.3
作者：
Carter, L L;Murphy, K M
通讯作者：
Murphy, K M
DOI：
10.1038/nri2580
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Smeltz, Ronald B.
通讯作者：
Smeltz, Ronald B.
影响因子：
4.4
作者：
Kabelitz, D;Wesch, D;Zöller, M
通讯作者：
Zöller, M
影响因子：
6.6
作者：
Liu, ZY;Guo, BL;Lopez, RD
通讯作者：
Lopez, RD