αβγδ T cells play a vital role in fetal human skin development and immunity

J Exp Med. 2021 Apr 5;218(4):e20201189. doi: 10.1084/jem.20201189.

Abstract

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor-ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytokines / metabolism
  • Fetus / immunology*
  • Healthy Volunteers
  • Humans
  • Immunologic Surveillance*
  • Intestines / embryology
  • Intestines / immunology
  • Middle Aged
  • RNA-Seq / methods
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Single-Cell Analysis / methods
  • Skin / embryology*
  • Skin / growth & development
  • Skin / immunology*
  • T-Lymphocytes / immunology*
  • Transcriptome

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta