Human blood MAIT cell subsets defined using MR1 tetramers.

Human blood MAIT cell subsets defined using MR1 tetramers.
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DOI:
10.1111/imcb.12021
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发表时间:
2018-05
影响因子:
4
通讯作者:
Godfrey DI
Godfrey DI
中科院分区:
医学3区
文献类型:
--
作者:
Gherardin NA;Souter MN;Koay HF;Mangas KM;Seemann T;Stinear TP;Eckle SB;Berzins SP;d'Udekem Y;Konstantinov IE;Fairlie DP;Ritchie DS;Neeson PJ;Pellicci DG;Uldrich AP;McCluskey J;Godfrey DI

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粘液相关的不变T(MAIT)细胞占循环人类T细胞的10%。它们通常使用非谱系特异性(替代)标志物的组合来定义,如抗TRAV 1 - 2、CD 161、IL-18 R α和CD 26。MR 1-Ag四聚体的开发现在允许基于T细胞受体特异性特异性识别MAIT细胞。在这里,我们比较了这些方法用于识别MAIT细胞,并表明替代标志物并不总是准确地识别这些细胞,特别是CD 4+部分。此外,虽然所有MAIT细胞亚群产生的IFNγ、TNF和IL-17 A水平相当,但CD 4+细胞群产生的IL-2比其他亚群多。在人类个体发育研究中,我们发现,大多数MR 1四聚体+ MAIT细胞的频率,除了CD 4 + MAIT细胞,从出生到25岁左右增加,此后下降。我们还证明了MAIT细胞和其他非常规T细胞(包括自然杀伤T(NKT)细胞和Vδ2+ γδ T细胞)的频率之间的正相关性。因此,这项研究表明,MAIT细胞在表型和功能上是多样的,替代标志物可能无法可靠地识别所有这些细胞,并且它们的数量以年龄依赖性方式调节,并与NKT和Vδ2+ γδ T细胞相关。
Mucosal‐associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non‐lineage‐specific (surrogate) markers such as anti‐TRAV1‐2, CD161, IL‐18Rα and CD26. The development of MR1‐Ag tetramers now permits the specific identification of MAIT cells based on T‐cell receptor specificity. Here, we compare these approaches for identifying MAIT cells and show that surrogate markers are not always accurate in identifying these cells, particularly the CD4+ fraction. Moreover, while all MAIT cell subsets produced comparable levels of IFNγ, TNF and IL‐17A, the CD4+ population produced more IL‐2 than the other subsets. In a human ontogeny study, we show that the frequencies of most MR1 tetramer+ MAIT cells, with the exception of CD4+ MAIT cells, increased from birth to about 25 years of age and declined thereafter. We also demonstrate a positive association between the frequency of MAIT cells and other unconventional T cells including Natural Killer T (NKT) cells and Vδ2+ γδ T cells. Accordingly, this study demonstrates that MAIT cells are phenotypically and functionally diverse, that surrogate markers may not reliably identify all of these cells, and that their numbers are regulated in an age‐dependent manner and correlate with NKT and Vδ2+ γδ T cells.
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