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

N Li, V van Unen, T Abdelaal, N Guo… - Nature …, 2019 - nature.com
N Li, V van Unen, T Abdelaal, N Guo, SA Kasatskaya, K Ladell, JE McLaren, ES Egorov
Nature immunology, 2019nature.com
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 …
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.
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