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

Nature immunology, 2019-03, Vol.20 (3), p.301-312 [Peer Reviewed Journal]

2019© The Author(s), under exclusive licence to Springer Nature America, Inc. 2019 ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. ;ISSN: 1529-2908 ;EISSN: 1529-2916 ;DOI: 10.1038/s41590-018-0294-9 ;PMID: 30664737

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Title:
Memory CD4 + T cells are generated in the human fetal intestine
Author: 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
Subjects: Antigen-presenting cells ; Antigen-Presenting Cells - cytology ; Antigen-Presenting Cells - immunology ; Antigen-Presenting Cells - metabolism ; Antigens ; Avidity ; CD4 antigen ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD5 antigen ; CD5 Antigens - genetics ; CD5 Antigens - immunology ; CD5 Antigens - metabolism ; Cell division ; Cells, Cultured ; Cytokines ; Cytometry ; Exposure ; Fetus - cytology ; Fetus - immunology ; Fetus - metabolism ; Fetuses ; Flow Cytometry ; Gene Expression Profiling - methods ; Gene Expression Regulation, Developmental - immunology ; High-Throughput Nucleotide Sequencing ; Humans ; Immunologic Memory - genetics ; Immunologic Memory - immunology ; Immunological memory ; Immunophenotyping ; Inflammation ; Interleukin 2 ; Intestine ; Intestines - cytology ; Intestines - embryology ; Intestines - immunology ; Ki-67 Antigen - genetics ; Ki-67 Antigen - immunology ; Ki-67 Antigen - metabolism ; Lymphocytes ; Lymphocytes T ; Memory cells ; Ribonucleic acid ; RNA ; Subpopulations ; T cell receptors ; Transcription ; γ-Interferon
Is Part Of: Nature immunology, 2019-03, Vol.20 (3), p.301-312
Description: 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1529-2908
EISSN: 1529-2916
DOI: 10.1038/s41590-018-0294-9
PMID: 30664737
Source: AUTh Library subscriptions: ProQuest Central
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Memory CD4 + T cells are generated in the human fetal intestine

2019© The Author(s), under exclusive licence to Springer Nature America, Inc. 2019 ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. ;ISSN: 1529-2908 ;EISSN: 1529-2916 ;DOI: 10.1038/s41590-018-0294-9 ;PMID: 30664737

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