Memory CD4+ T cells are generated in the human fetal intestine
Memory CD4+ T cells are generated in the human fetal intestine
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DOI：
10.1038/s41590-018-0294-9
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发表时间：
2019-03-01
影响因子：
30.5
通讯作者：
Koning, Frits
中科院分区：
文献类型：
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作者：
Li, Na;van Unen, Vincent;Koning, Frits
胎儿被认为是保护暴露于外来抗原，但CD 45 RO（+）T细胞驻留在胎儿肠道。在这里，我们将功能测定与质谱细胞术、单细胞RNA测序和高通量T细胞抗原受体（TCR）测序相结合，以表征人胎儿肠道中的CD 4（+）T细胞区室。我们鉴定了22个CD 4（+）T细胞簇，包括幼稚样、调节样和记忆样亚群，这些亚群在转录水平上得到了证实和进一步表征。记忆样CD 4（+）T细胞具有高表达Ki-67（指示细胞分裂）和CD 5（TCR亲合力的替代标志物），并产生细胞因子IFN-γ和IL-2。通路分析揭示了与细胞活化和促炎效应子功能相关的分化轨迹，TCR库分析表明了克隆扩增、独特的库特征和记忆样CD 4（+）T细胞亚群之间的相互联系。成像质量细胞仪显示记忆样CD 4（+）T细胞与抗原呈递细胞共定位。总的来说，这些结果为人类胎儿肠道中记忆样CD 4（+）T细胞的产生提供了证据，这与暴露于外源抗原一致。
The fetus is thought to be protected from exposure to foreign antigens, yet CD45RO(+) T cells reside in the fetal intestine. Here we combined functional assays with mass cytometry, single-cell RNA sequencing and high-throughput T cell antigen receptor (TCR) sequencing to characterize the CD4(+) T cell compartment in the human fetal intestine. We identified 22 CD4(+) T cell clusters, including naive-like, regulatory-like and memory-like subpopulations, which were confirmed and further characterized at the transcriptional level. Memory-like CD4(+) T cells had high expression of Ki-67, indicative of cell division, and CD5, a surrogate marker of TCR avidity, and produced the cytokines IFN-gamma and IL-2. Pathway analysis revealed a differentiation trajectory associated with cellular activation and proinflammatory effector functions, and TCR repertoire analysis indicated clonal expansions, distinct repertoire characteristics and interconnections between subpopulations of memory-like CD4(+) T cells. Imaging mass cytometry indicated that memory-like CD4(+) T cells colocalized with antigen-presenting cells. Collectively, these results provide evidence for the generation of memory-like CD4(+) T cells in the human fetal intestine that is consistent with exposure to foreign antigens.