γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis

J Exp Med. 2024 Jul 1;221(7):e20231987. doi: 10.1084/jem.20231987. Epub 2024 May 16.

Abstract

Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.

MeSH terms

  • Adult
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • CD83 Antigen*
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature* / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Neonatal Sepsis / immunology
  • Receptors, Antigen, T-Cell, gamma-delta* / immunology
  • Receptors, Antigen, T-Cell, gamma-delta* / metabolism
  • Sepsis / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism