Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes
Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes
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DOI：
10.1016/j.exphem.2009.01.010
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发表时间：
2009-05-01
影响因子：
2.6
通讯作者：
Introna, Martino
中科院分区：
文献类型：
--
作者：
Franceschetti, Marta;Pievani, Alice;Introna, Martino
Objective.细胞因子诱导的杀伤细胞（CIK）是具有自然杀伤（NK）样细胞毒活性的CD 3（+）CD 56（+）T细胞，用于肿瘤的免疫治疗。我们的目的是充分表征CIK细胞并定义它们的个体发生。通过用干扰素-γ、抗-CD 3和白细胞介素-2刺激外周血单个核细胞或T细胞亚群在体外产生CIK。它们在表型、细胞毒活性和CIK培养物中存在的循环CD 3（+）CD 56（+）细胞、NK细胞和CD 56（-）T细胞的基因表达方面得到充分表征。CIK是由增殖的CD 3（+）CD 56（-）CD 8（+）T细胞分化而来的终末分化的CD 8 T细胞。它们表达多克隆T细胞受体V β链，并具有获得性CD 56、NKG 2D和大颗粒淋巴细胞形态，但缺乏大多数NK特异性活化（NKp 30、NKp 44、NKp 46）和抑制（KIR 2DL 1、KIR 2DL 2、KIR 3DLI、NKG 2A）的表达。CD 94）受体，并且可以杀死K562靶点。循环中的CD 3（+）CD 56（+）细胞也是CD 8（+）CD 16（-）细胞，但为寡克隆细胞，对K562的细胞毒性较差，表达较低水平的CD 56和NKG 2D。培养结束时存在的CIK、CD 56（-）T和NK细胞的基因分析表明，与CIK和NK细胞相比，CIK和CD 56（-）T之间的差异要有限得多。与CD 56（-）T细胞相比，CIK细胞中上调的大多数基因是肿瘤坏死因子基因网络的一部分。CIK表型，即CD 45 RA（+）、CCR 7（-）、CD 62 L-弱阳性、CD 11 a（+）、CD 27（+）、CD 28（-）、巨噬细胞炎性蛋白1 α（+）、穿孔素（+）、Fas配体（+），几乎完全与终末分化的人记忆T细胞的TRA（+）效应记忆CD 27单阳性亚群所描述的一致。(c)2009 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Objective. Cytokine-induced killer cells (CIK) are CD3(+)CD56(+) T cells with natural killer (NK)-like cytotoxic activity used for the immunotherapy of tumors. We aimed to fully characterize CIK cells and define their ontogeny.Materials and Methods. CIK were generated in vitro by stimulation of peripheral blood mononuclear cells or T-cell subsets with interferon-gamma, anti-CD3 and interleukin-2. They were fully characterized in terms of phenotype, cytotoxic activity, and gene expression with respect to circulating CD3(+)CD56(+) cells, NK cells, and CD56(-) T cells present in CIK cultures.Results. We demonstrate that CIK are terminally differentiated CD8 T cells that derive from proliferating CD3(+)CD56(-)CD8(+) T cells. They express polyclonal T-cell receptor V beta chains and have acquired CD56, NKG2D, and large granular lymphocyte morphology, but lack expression of most NK-specific activating (NKp30, NKp44, NKp46) and inhibitory (KIR2DL1, KIR2DL2, KIR3DLI, NKG2A. CD94) receptors, and can kill K562 targets. Circulating CD3(+)CD56(+) cells are also CD8(+)CD16(-), but are oligoclonal, poorly cytotoxic for K562, and express lower levels of CD56 and NKG2D. Gene profiling of CIK, CD56(-) T and NK cells present at the end of culture shows that differences are much more limited between CIK and CD56(-) T compared to CIK and NK cells. Most of the genes upregulated in CIK cells compared to CD56(-) T cells are part of the tumor necrosis factor gene network.Conclusions. The CIK phenotype, that is CD45RA(+), CCR7(-), CD62L-weakly positive, CD11a(+), CD27(+), CD28(-), macrophage inflammatory protein 1 alpha(+), perforin(+), Fas ligand(+) coincides almost exactly with that described for the T RA(+) effector memory CD27 single positive subset of terminally differentiated human memory T cells. (c) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.