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

Preterm infants are at high risk of developing neonatal sepsis. gamma delta T cells are thought to be an important set of effector cells in neonates. Here, gamma delta 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 V gamma 9V delta 2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived V gamma 9V delta 2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DR(hi)CD83(+) gamma delta T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated V gamma 9V delta 2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult V gamma 9V delta 2 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 gamma delta T cells after preterm birth and highlight their phenotypic diversity in infections.