Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire
Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire
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DOI：
10.1073/pnas.1412058112
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发表时间：
2015-02-10
影响因子：
11.1
通讯作者：
Vermijlen, David
中科院分区：
文献类型：
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作者：
Dimova, Tanya;Brouwer, Margreet;Vermijlen, David
δ T细胞是一种非传统的T细胞，它通过δ T细胞受体（TCR）识别抗原，其方式与传统的α - β T细胞有着根本的不同。δ T细胞通常根据它们在TCR中表达的v - γ和/或v - δ链的类型分为亚群。表达含有γ链可变区9和δ链可变区2的TCR的T细胞（V γ γ 9V δ 2 T细胞）是成人外周血中主要的γ δ T细胞亚群。目前的想法是，这种优势是出生后细胞扩增的结果，表达特定的互补决定区3 (CDR3)，以应对与微生物的接触，特别是那些产生来自类异戊二烯合成的2- c -甲基- d -赤藓糖醇4-磷酸途径的磷酸抗原。然而，本研究表明，在妊娠中期，V δ 1（+）和V δ 3(+) γ δ T细胞仅以低频率存在，而不需要产后微生物暴露，V δ 9V δ 2 T细胞是妊娠中期胎儿的主要血液亚群。胎儿血V γ 9V δ 2 T细胞对磷抗原有应答性，在V γ 9链基因的CDR3中表现出非常有限的多样性，其中种系编码序列占所有序列的50%，与原型CDR3 δ 2相关。此外，这些胎儿血液V γ 9V δ 2 T细胞在功能上是预先编程的（例如，ifn - γ和颗粒酶- a /K），具有快速激活的先天样T细胞的特性。因此，磷抗原反应效应T细胞的富集发生在胎儿出生后的微生物暴露之前。这些不同的特征已经在小鼠中与选择元素的行为联系起来，并且将在人类和小鼠γ δ T细胞之间建立比通常所表达的更强的相似性。
gamma delta T cells are unconventional T cells recognizing antigens via their gamma delta T-cell receptor (TCR) in a way that is fundamentally different from conventional alpha beta T cells gamma delta T cells usually are divided into subsets according the type of V-gamma and/or V-delta chain they express in their TCR. T cells expressing the TCR containing the gamma-chain variable region 9 and the delta-chain variable region 2 (V gamma 9V delta 2 T cells) are the predominant gamma delta T-cell subset in human adult peripheral blood. The current thought is that this predominance is the result of the postnatal expansion of cells expressing particular complementarydetermining region 3 (CDR3) in response to encounterswithmicrobes, especially those generating phosphoantigens derived from the 2-C-methyl- D-erythritol 4-phosphate pathway of isoprenoid synthesis. However, here we show that, rather than requiring postnatal microbial exposure, V gamma 9V delta 2 T cells are the predominant blood subset in the second-trimester fetus, whereas V delta 1(+) and V delta 3(+) gamma delta T cells are present only at low frequencies at this gestational time. Fetal blood V gamma 9V delta 2 T cells are phosphoantigen responsive and display very limited diversity in the CDR3 of the V gamma 9 chain gene, where a germline- encoded sequence accounts for >50% of all sequences, in association with a prototypic CDR3 delta 2. Furthermore, these fetal blood V gamma 9V delta 2 T cells are functionally preprogrammed (e.g., IFN-gamma nd granzymes-A/K), with properties of rapidly activatable innatelike T cells. Thus, enrichment for phosphoantigen-responsive effector T cells has occurred within the fetus before postnatal microbial exposure. These various characteristics have been linked in the mouse to the action of selecting elements and would establish a much stronger parallel between human and murine gamma delta T cells than is usually articulated.