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Cited by 168

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Memory CD4+ T cells are generated in the human fetal intestine

Open access
Li, Na, van Unen, Vincent, Abdelaal, Tamim, Guo, Nannan, Kasatskaya, Sofya A., Ladell, Kristin, McLaren, James E., Egorov, Evgeny S., Izraelson, Mark, Chuva de Sousa Lopes, Susana M., Höllt, Thomas, Britanova, Olga V, Eggermont, Jeroen, de Miranda, Noel F. C. C., Chudakov, Dmitriy M., Price, David A., Lelieveldt, Boudewijn P. F., Koning, Frits·2019·Nature Immunology

Abstract

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-γ 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. Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4+ T cell compartment in the human fetal intestine.

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Metadata

Authors
Li, N., van Unen, V., Abdelaal, T., Guo, N., Kasatskaya, S. A., Ladell, K., McLaren, J. E., Egorov, E. S., Izraelson, M., Chuva de Sousa Lopes, S. M., Höllt, T., Britanova, O. V., Eggermont, J., de Miranda, N. F. C. C., Chudakov, D. M., Price, D. A., Lelieveldt, B. P. F., & Koning, F.
Venue
Nature Immunology
Published
2019-01-21
Volume
20
Issue
3
Pages
301-312
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2909781249
Cited by
168
References
7
FWCI
8.33
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Memory CD4+ T cells are generated in the human fetal intestine. https://app.cochat.ai/papers/10.1038/s41590-018-0294-9
The paper
Li, N., van Unen, V., Abdelaal, T., Guo, N., Kasatskaya, S. A., Ladell, K., McLaren, J. E., Egorov, E. S., Izraelson, M., Chuva de Sousa Lopes, S. M., Höllt, T., Britanova, O. V., Eggermont, J., de Miranda, N. F. C. C., Chudakov, D. M., Price, D. A., Lelieveldt, B. P. F., & Koning, F. (2019). Memory CD4+ T cells are generated in the human fetal intestine. Nature Immunology. https://doi.org/10.1038/s41590-018-0294-9

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.