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

Journal article (2019)

Authors

Na Li Leiden University Medical Center
Vincent van Unen Leiden University Medical Center
T.R.M. Abdelaal Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
Nannan Guo Leiden University Medical Center
Sofya A. Kasatskaya Skolkovo Institute of Science and Technology, Russian Academy of Sciences
S.M. Chuva de Sousa Lopes Leiden University Medical Center
T. Höllt Leiden University Medical Center, Computer Graphics and Visualisation - EEMCS
Olga V. Britanova Russian Academy of Sciences
Boudewijn Lelieveldt Pattern Recognition and Bioinformatics - EEMCS , Leiden University Medical Center
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Research Group
Pattern Recognition and Bioinformatics (EEMCS) (TU Delft)
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Published Date

2019

Language

English

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Faculty

Electrical Engineering, Mathematics and Computer Science

Department

Intelligent Systems

Research Group

Pattern Recognition and Bioinformatics

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.