The generation of human gammadelta T cell repertoires during fetal development.
The generation of human gammadelta T cell repertoires during fetal development.
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DOI：
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发表时间：
1998
影响因子：
4.4
通讯作者：
L. McVay;S. Jaswal;C. Kennedy;A. Hayday;S. Carding
中科院分区：
文献类型：
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作者：
L. McVay;S. Jaswal;C. Kennedy;A. Hayday;S. Carding
人类γ δ T细胞如何正常产生的性质尚不清楚。我们已经使用RT-PCR分析和DNA测序来鉴定和比较在胎儿肠道、肝脏和胸腺中从头产生的δ编码的TCR（TCRD），并确定在正常胚胎发育期间何时、何地以及如何建立TCRD库。重排的TCRDV基因首先在妊娠6至9周之间在胸腺外的肝脏和原肠中表达。虽然DV 1 Rs和/或DV 2 Rs占主导地位，TCRDV基因重排和转录在个体发育过程中的每个组织中的模式的差异进行了鉴定。特异性的，DV 2编码的TCR在来自相同和遗传上不同的供体的组织中在整个个体发育中高度保守。虽然胸腺和肠道γ δ T细胞库在发育早期部分重叠，但它们在孕中期分化并变得不重叠，并且肠道γ δ T细胞库的产生的特征在于DV 1 Rs和DV 2 Rs处理的差异。而DV 1 Rs的结构多样性在肠道发育过程中逐渐增加，直到出生，DV 2 Rs在整个个体发育过程中具有有限的结构多样性。总之，我们的发现为不同胎儿组织支持γ δ T细胞发育的能力提供了证据。
The nature of how human gammadelta T cells are normally generated is not clear. We have used an RT-PCR assay and DNA sequencing to identify and compare delta-encoded TCRs (TCRDs) that are generated de novo in the fetal gut, liver, and thymus and to determine when, where, and how the TCRD repertoire is established during normal embryonic development. Rearranged TCRDV genes are first expressed outside of the thymus in the liver and primitive gut between 6 and 9 wk gestation. Although DV1Rs and/or DV2Rs predominated, differences in the pattern of TCRDV gene rearrangement and transcription in each tissue during ontogeny were identified. Specific, DV2-encoded TCRs are highly conserved throughout ontogeny in the tissues from the same and between genetically distinct donors. Although the thymic and intestinal gammadelta T cell repertoires partially overlap early in development, they diverge and become nonoverlapping during the second trimester, and the generation of the intestinal gammadelta T cell repertoire is characterized by differences in the processing of DV1Rs and DV2Rs. Whereas the structural diversity of DV1Rs progressively increases during gut development up to birth, DV2Rs have limited structural diversity throughout ontogeny. Together, our findings provide evidence for the ability of different fetal tissues to support the development of gammadelta T cells.