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

Na Li, Vincent van Unen, Tamim Abdelaal, Nannan Guo, Sofya A. Kasatskaya, Susana M. Chuva de Sousa Lopes, Thomas Höllt, Olga V. Britanova, Boudewijn P.F. Lelieveldt, More Authors

Research output: Contribution to journalArticleScientificpeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)301-312
Number of pages12
JournalNature Immunology
Volume20
Issue number3
DOIs
Publication statusPublished - 2019

Fingerprint Dive into the research topics of 'Memory CD4<sup>+</sup> T cells are generated in the human fetal intestine'. Together they form a unique fingerprint.

  • Cite this

    Li, N., van Unen, V., Abdelaal, T., Guo, N., Kasatskaya, S. A., Chuva de Sousa Lopes, S. M., Höllt, T., Britanova, O. V., Lelieveldt, B. P. F., & More Authors (2019). Memory CD4+ T cells are generated in the human fetal intestine. Nature Immunology, 20(3), 301-312. https://doi.org/10.1038/s41590-018-0294-9