Memory CD4 T cells are generated in the human fetal intestine.
Na Li, Vincent van Unen, Tamim Abdelaal, Nannan Guo, Sofya A Kasatskaya, Kristin Ladell, James E McLaren, Evgeny S Egorov, Mark Izraelson, Susana M Chuva de Sousa Lopes, Thomas Höllt, Olga V Britanova, Jeroen Eggermont, Noel F C C de Miranda, Dmitriy M Chudakov, David A Price, Boudewijn P F Lelieveldt, Frits Koning
Author Information
Na Li: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands. ORCID
Vincent van Unen: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands. ORCID
Tamim Abdelaal: Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.
Nannan Guo: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Sofya A Kasatskaya: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Kristin Ladell: Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. ORCID
James E McLaren: Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
Evgeny S Egorov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Mark Izraelson: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Susana M Chuva de Sousa Lopes: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands. ORCID
Thomas Höllt: Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.
Olga V Britanova: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Jeroen Eggermont: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Noel F C C de Miranda: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Dmitriy M Chudakov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
David A Price: Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. ORCID
Boudewijn P F Lelieveldt: Department of Pattern Recognition and Bioinformatics Group, Delft University of Technology, Delft, the Netherlands.
Frits Koning: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands. F.Koning@lumc.nl. ORCID
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.
