CD38 expression by neonatal human naive CD4+ T cells shapes their distinct metabolic and tolerogenic properties
Publication date
2026-04-15
Authors
Dwyer, Laura R
DeRogatis, Andrea M
Clancy, Sean
Gouirand, Victoire
Chien, Charles
Rogers, Elizabeth E
Oltman, Scott P
Jelliffe-Pawlowski, Laura L
van den Broek, Theo
van Wijk, Femke
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Advisors
Supervisors
Document Type
Article
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Abstract
Neonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion of naive CD4+ T cells into Tregs. We demonstrated heightened capacity for FOXP3 expression and tolerogenic function among cord blood versus adult blood naive CD4+ T cells. Further, this was linked to a distinct cord blood metabolic profile and elevated neonatal expression of the NADase, CD38. Early-life naive CD4+ T cells demonstrated a metabolic preference for glycolysis, which directly facilitated their differentiation trajectory. We revealed an age-dependent gradient in CD38 levels on naive CD4+ T cells and showed that high CD38 expression contributes to the glycolytic state and tolerogenic potential of neonatal CD4+ T cells, effects mediated at least partly via the NAD-dependent deacetylase SIRT1. Thus, the early-life window for peripheral tolerance in humans is critically enabled by the immunometabolic state of the naive CD4+ compartment.
Keywords
Development, Immunology, Metabolism, T cell development, Tolerance, Tregs, General Medicine
Citation
Dwyer, L R, DeRogatis, A M, Clancy, S, Gouirand, V, Chien, C, Rogers, E E, Oltman, S P, Jelliffe-Pawlowski, L L, van den Broek, T, van Wijk, F, Lynch, S V, Rutishauser, R L, Wagner, A, Combes, A J & Scharschmidt, T C 2026, 'CD38 expression by neonatal human naive CD4+ T cells shapes their distinct metabolic and tolerogenic properties', The Journal of clinical investigation, vol. 136, no. 8. https://doi.org/10.1172/JCI200062