Type 1 diabetes progression is associated with loss of CD3+CD56+ regulatory T cells that control CD8+ T-cell effector functions

Giuseppe Terrazzano, Sara Bruzzaniti, Valentina Rubino, Marianna Santopaolo, Anna Teresa Palatucci, Angela Giovazzino, Claudia La Rocca, Paola de Candia, Annibale Puca, Francesco Perna, Claudio Procaccini, Veronica De Rosa, Chiara Porcellini, Salvatore De Simone, Valentina Fattorusso, Antonio Porcellini, Enza Mozzillo, Riccardo Troncone, Adriana Franzese, Johnny LudvigssonGiuseppe Matarese, Giuseppina Ruggiero, Mario Galgani

Research output: Contribution to journalLetterpeer-review


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 coexpression of CD3 and CD56 molecules (TR3-56), is reduced in individuals 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 beta-cell function and with the presence of diabetic ketoacidosis. Since autoreactive CD8+ T cells mediate disruption of insulin-producing beta cells1–3, we demonstrate that TR3-56 cells can suppress CD8+ T cell functions in vitro by reducing the levels of intracellular reactive oxygen species. The suppressive function, phenotype and transcriptional signature of TR3-56 cells are also altered in children with T1D. 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.

Original languageEnglish
Pages (from-to)142-152
Number of pages11
JournalNature Metabolism
Issue number2
Publication statusPublished - Feb 1 2020

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Internal Medicine
  • Cell Biology

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