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

Li, Na, van Unen, Vincent, Abdelaal, Tamim, Guo, Nannan, Kasatskaya, Sofya A., Ladell, Kristin ORCID:, McLaren, James E. ORCID:, 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. ORCID:, Lelieveldt, Boudewijn P. F. and Koning, Frits 2019. Memory CD4+ T cells are generated in the human fetal intestine. Nature Immunology 20 , pp. 301-312. 10.1038/s41590-018-0294-9

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of First Compliant Deposit: 8 February 2019
Date of Acceptance: 4 December 2018
Last Modified: 17 Nov 2023 12:45

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