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  • Terrazzano, Giuseppe, et al. (author)
  • T1D progression is associated with loss of CD3+CD56+ regulatory T cells that control CD8+ T cell effector functions
  • 2020
  • In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:2, s. 142-152
  • Journal article (peer-reviewed)abstract
    • An unresolved issue in autoimmunity is the lack of surrogate biomarkers of immunological self-tolerance for disease monitoring. Here, we show that peripheral frequency of a regulatory T cell population, characterized by the co-expression of CD3 and CD56 molecules (TR3-56), is reduced in subjects with new-onset type 1 diabetes (T1D). In three independent T1D cohorts, we find that low frequency of circulating TR3-56 cells is associated with reduced β-cell function and with the presence of diabetic ketoacidosis. As autoreactive CD8+ T cells mediate disruption of insulin-producing β-cells1-3, we demonstrate that TR3-56 cells can suppress CD8+ T cell functions in vitro by reducing levels of intracellular reactive oxygen species. The suppressive function, phenotype and transcriptional signature of TR3-56 cells are also altered in T1D children. Together, our findings indicate that TR3-56 cells constitute a regulatory cell population that controls CD8+ effector functions, whose peripheral frequency may represent a traceable biomarker for monitoring immunological self-tolerance in T1D.
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