期刊
NATURE IMMUNOLOGY
卷 20, 期 3, 页码 301-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-018-0294-9
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- Leiden University Medical Center
- Netherlands Organization for Scientific Research (NWO Applied Technical Sciences) [12721]
- Netherlands Organization for Scientific Research (ZonMW) [91112008]
- Russian Science Foundation [16-15-00149]
- Wellcome Trust [100326/Z/12/Z]
- European Commission under an MSCA-ITN award [675743/ISPIC]
- China Scholarship Council
- Russian Science Foundation [16-15-00149] Funding Source: Russian Science Foundation
- Wellcome Trust [100326/Z/12/Z] Funding Source: researchfish
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.
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