FcγRIII discriminates between 2 subsets of Vγ9Vδ2 effector cells with different responses and activation pathways

FcγRIII discriminates between 2 subsets of Vγ9Vδ2 effector cells with different responses and activation pathways
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DOI:
10.1182/blood-2004-01-0331
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发表时间:
2004-09-15
期刊:
影响因子:
20.3
通讯作者:
Battistini, L
Battistini, L
中科院分区:
医学1区
文献类型:
--
作者:
Angelini, DF;Borsellino, G;Battistini, L

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在识别非肽磷酸抗原后,人 Vdelta2 T 淋巴细胞进入谱系分化模式,决定具有一系列效应功能的记忆细胞的产生。在这里,我们表明,在效应记忆 Vdelta2 群体中,可以识别出关于表型、激活模式和反应类型的 2 个不同且互补的子集:Vdelta2 T-EMh 细胞,表达高水平的趋化因子受体,但表达低水平的穿孔素和自然杀伤受体 (NKR),并产生大量的干扰素 γ (IFN-γ) 和肿瘤坏死 因子 a (TNF-α) 响应磷酸抗原的 T 细胞受体 (TCR) 特异性刺激; Vdelta2 T-EMRA 细胞组成型表达多种 NKR、大量穿孔素,但趋化因子受体和 IFN-γ 水平较低。这些 NK 样细胞对磷酸抗原具有抵抗力,但对 FcgammaRIII (CD16) 的激活作出反应,并且对肿瘤靶细胞具有高度活性。因此,循环Vdelta2 T淋巴细胞包含2个功能不同的效应记忆细胞亚群,可以根据CD16表达来区分它们。 (C) 2004 年,美国血液学会。
Upon recognition of nonpeptidic phos-phoantigens, human Vdelta2 T lymphocytes enter a lineage differentiation pattern that determines the generation of memory cells with a range of effector functions. Here, we show that within the effector memory Vdelta2 population, 2 distinct and complementary subsets with regard to phenotype, mode of activation, and type of responses can be identified: Vdelta2 T-EMh cells, which express high levels of chemo-kine receptors, but low levels of perforin and of natural killer receptors (NKRs) and which produce large amounts of interferon gamma (IFN-gamma) and tumor necrosis factor a (TNF-alpha) in response to T-cell receptor (TCR)-specific stimulation by phosphoantigens; and Vdelta2 T-EMRA cells, which constitutively express several NKRs, high amounts of perforin, but low levels of chemokine receptors and of IFN-gamma. These NK-like cells are refractory to phosphoantigen but respond to activation via FcgammaRIII (CD16) and are highly active against tumoral target cells. Thus, circulating Vdelta2 T lymphocytes comprise 2 functionally diverse subsets of effector memory cells that may be discriminated on the basis of CD16 expression. (C) 2004 by The American Society of Hematology.