Development of V alpha 14(+) NK T cells in the early stages of embryogenesis

Development of V alpha 14(+) NK T cells in the early stages of embryogenesis
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DOI:
10.1073/pnas.93.13.6516
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发表时间:
1996-06-25
影响因子:
11.1
通讯作者:
Taniguchi, M
Taniguchi, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Makino, Y;Kanno, R;Taniguchi, M

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大多数T淋巴细胞在妊娠约第15天(d15) - 第17天开始在胸腺中发育,并构成以外周多态性T细胞抗原受体(TCR)表达为特征的外周细胞库。与这些常规T细胞不同,一类被称为自然杀伤(NK)T细胞的T细胞亚群(其中大多数表达由Vα14Jα281基因编码且带有1个核苷酸N区的不变TCR)优先在胸腺外分化,并在高频下主导外周T细胞群(在脾脏T细胞中占5%,在骨髓T细胞中占40%)。在此,我们研究了NK T细胞的发育,发现不变的Vα14⁺ TCR转录本以及由Vα14和Jα281基因重排产生的环状DNA在妊娠第9.5天的胚胎体以及妊娠第11.5 - 13.5天的卵黄囊和胎肝中可被检测到,但在胸腺中未检测到,而具有Vα1⁺ TCR表达的T细胞(胸腺中的主要群体)在这些妊娠早期阶段未被观察到。荧光激活细胞分选分析还表明,在早期胚胎发生过程中存在CD3⁺αβ⁺ T细胞,几乎所有这些细胞都是Vα14/Vβ8⁺ T细胞。据我们所知,这首次证明了在胚胎发生的早期阶段,一个T淋巴细胞亚群在胸腺外组织中发育。
The majority of T lymphocytes start to develop at around day 15 of gestation (d15)-d17 in the thymus and comprise the peripheral repertoire characterized by the expression of polymorphic T-cell antigen receptors (TCRs). Contrary to these conventional T cells, a subset of T cells, called natural killer (NK) T cells (most of them expressing an invariant TCR encoded by the V alpha 14J alpha 281 gene with a 1-nt N-region), preferentially differentiates extrathymically and dominates the peripheral T-cell population at a high frequency (5% in splenic T cells and 40% in bone marrow T cells). sere, we investigated the development of NK T cells and found that the invariant V alpha 14(+) TCR transcripts and the circular DNA created by V alpha 14 and J alpha 281 gene rearrangements can be detected in the embryo body at d9.5 of gestation and in the yolk sac and the fetal liver at d11.5-d13.5 of gestation, but not in the thymus, whereas T cells with V alpha 1(+) TCR expression, a major population in the thymus, were not observed at these early stages of gestation, Fluorescence-activated cell sorter analysis also demonstrated that there exist CD3(+) alpha beta(+) T cells, almost all of which are V alpha 14/V beta 8(+) T cells, during early embryogenesis. To our knowledge, this demonstrates for the first time that a T lymphocyte subset develops in extrathymic tissues during the early stages of embryogenesis.