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表达IgG Fc受体(CD16/Leu-11抗原)的细胞毒性CD3+ T淋巴细胞独特亚群的功能特性。

Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).

作者信息

Lanier L L, Kipps T J, Phillips J H

出版信息

J Exp Med. 1985 Dec 1;162(6):2089-106. doi: 10.1084/jem.162.6.2089.

Abstract

A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.

摘要

已鉴定、分离并对共表达CD3和IgG Fc受体(FcR)(CD16/Leu-11抗原)的外周血T淋巴细胞亚群进行了功能表征。使用含白细胞介素2(IL-2)的生长培养基对CD3+、CD16+细胞进行短期培养。新鲜分离的细胞和培养的细胞系均稳定表达CD3+、CD16+表型。此外,这些T细胞中的大多数缺乏CD4或CD8表达。与体外激活的细胞毒性T淋巴细胞和自然杀伤(NK)细胞一样,CD3+、CD16+细胞显示出许多嗜天青颗粒。尽管这些细胞即使在用IL-2刺激后也未能介导显著水平的NK细胞介导的细胞毒性,但它们有效地发挥了抗体依赖性细胞毒性(ADCC)效应细胞的作用。使用鼠抗HLA单克隆抗体(mAb)的同种型转换变体家族分析了ADCC的Ig同种型特异性。与CD3-、CD16+ NK细胞群体相似,CD3+、CD16+ T细胞优先使用IgG2a抗体介导ADCC。当与NK敏感的肿瘤细胞系K562或NK不敏感的B淋巴母细胞系CCRF-SB共培养时,CD3+、CD16+细胞表现出增殖反应。抗IL-2受体抗体显著抑制了对CCRF-SB的反应,而对K562的反应仅部分减弱。抗CD3 mAb的存在也在CD3+、CD16+群体中诱导了细胞毒性,表明细胞毒性可通过CD3-T细胞抗原受体复合物的刺激触发。通过从正常健康个体的外周血中分离这些CD3+、CD16+细胞,得以广泛研究表达IgG FcR的这一独特T淋巴细胞亚群的形态、抗原表型和功能行为。

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