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Memory CD4+ T cells are generated in the human fetal intestine
N. Li, V. van Unen, T. Abdelaal, N. Guo, SA. Kasatskaya, K. Ladell, JE. McLaren, ES. Egorov, M. Izraelson, SM. Chuva de Sousa Lopes, T. Höllt, OV. Britanova, J. Eggermont, NFCC. de Miranda, DM. Chudakov, DA. Price, BPF. Lelieveldt, F. Koning,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
Wellcome Trust - United Kingdom
NLK
ProQuest Central
od 2000-07-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-07-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-07-01 do Před 1 rokem
- MeSH
- antigen Ki-67 genetika imunologie metabolismus MeSH
- antigen prezentující buňky cytologie imunologie metabolismus MeSH
- antigeny CD5 genetika imunologie metabolismus MeSH
- CD4-pozitivní T-lymfocyty cytologie imunologie metabolismus MeSH
- imunofenotypizace MeSH
- imunologická paměť genetika imunologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- plod cytologie imunologie metabolismus MeSH
- průtoková cytometrie MeSH
- stanovení celkové genové exprese metody MeSH
- střeva cytologie embryologie imunologie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- vývojová regulace genové exprese imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Department of Anatomy and Embryology Leiden University Medical Center Leiden the Netherlands
Department of Pathology Leiden University Medical Center Leiden the Netherlands
Department of Radiology Leiden University Medical Center Leiden the Netherlands
Division of Infection and Immunity Cardiff University School of Medicine Cardiff UK
Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow Russia
Citace poskytuje Crossref.org
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