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首页> 外文OA文献 >Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11
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Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11

机译：使用新型不变性自然杀伤T细胞克隆型单克隆抗体6B11表征健康和疾病中人类不变性自然杀伤T亚群

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Identification of human CD1d-restricted T-cell receptor (TCR)-invariant natural killer T (iNKT) cells has been dependent on utilizing combinations of monoclonal antibodies or CD1d tetramers, which do not allow for the most specific analysis of this T-cell subpopulation. A novel monoclonal antibody (clone 6B11), specific for the invariant CDR3 loop of human canonical Vα24Jα18 TCR α chain, was developed and used to specifically characterize iNKT cells. In healthy individuals studied for up to 1 year, a wide but stable frequency of circulating iNKT cells (range: 0·01–0·92%) was observed, with no differences in frequency by gender. Four stable iNKT cell subsets were characterized in peripheral blood based on the expression of CD4 and CD8, with CD8+ iNKT cells being a phenotypic and functionally different subset from CD4+ and double negative iNKT cells; in particular, LAG-3 was preferentially expressed on CD8+ iNKT cells. In addition, a strong negative linear correlation between the frequency of total iNKT cells and percentage of the CD4+ subset was observed. In terms of their potential association with disease, patients at risk for type 1 diabetes had significantly expanded frequencies of double negative iNKT cells when compared to matched controls and first-degree relatives. Moreover, peripheral blood CD4+ iNKT cells were the highest producers of interleukin-4, while the production of interferon-γ and tumour necrosis factor-α was similar amongst all iNKT cell subsets. These differences in iNKT cell subsets suggest that in humans the relative ratio of iNKT cell subsets may influence susceptibility vs. resistance to immune-mediated diseases.
机译：鉴定人类CD1d限制性T细胞受体（TCR）不变的自然杀伤性T（iNKT）细胞一直依赖于单克隆抗体或CD1d四聚体的组合利用，这不允许对该T细胞亚群进行最具体的分析。开发了一种新的单克隆抗体（克隆6B11），其特异性针对人经典Vα24Jα18TCRα链的恒定CDR3环，并用于特异性表征iNKT细胞。在研究了长达1年的健康个体中，观察到循环中的iNKT细胞的频率范围广泛但稳定（范围：0·01-0·92％），但性别之间的频率没有差异。根据CD4和CD8的表达，在外周血中表征了四个稳定的iNKT细胞亚群，其中CD8 + iNKT细胞是与CD4 +和双阴性iNKT细胞表型和功能不同的亚群。特别地，LAG-3优先在CD8 + iNKT细胞上表达。另外，在总的iNKT细胞的频率和CD4 +亚群的百分比之间观察到强烈的负线性相关性。就与疾病的潜在关联而言，与匹配的对照和一级亲属相比，处于1型糖尿病风险中的患者的iNKT双阴性细胞的发生频率显着增加。此外，外周血CD4 + iNKT细胞是白细胞介素4的最高产量，而所有iNKT细胞亚群中干扰素-γ和肿瘤坏死因子-α的产量相似。 iNKT细胞亚群的这些差异表明，在人类中，iNKT细胞亚群的相对比例可能会影响易感性与对免疫介导疾病的抵抗力。

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