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T1D progression is associated with loss of CD3

Authors :
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, Ludvigsson
Giuseppe, Matarese
Giuseppina, Ruggiero
Mario, Galgani
Source :
Nature metabolism
Publication Year :
2020

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.

Details

ISSN :
25225812
Volume :
2
Issue :
2
Database :
OpenAIRE
Journal :
Nature metabolism
Accession number :
edsair.pmid..........9dc7354ec05eee6b6530b3c280fab593