Temporal Alterations in CD8+ T Cells During the Progression From Stage 1 to Stage 3 Type 1 Diabetes.
Diabetes
; 73(10): 1705-1715, 2024 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-38967999
ABSTRACT
CD8+ T cells are perceived to play a major role in the pathogenesis of type 1 diabetes (T1D). In this study, we characterized the function and phenotype of circulating CD8+ memory T cells in samples from individuals at different stages of T1D progression using flow cytometry and single-cell multiomics. We observed two distinct CD8+ T-cell signatures during progression of T1D within the highly differentiated CD27-CD8+ memory T-cell subset. A proinflammatory signature, with an increased frequency of IFN-γ+TNF-α+ CD27-CD8+ memory T cells, was observed in children with newly diagnosed T1D (stage 3) and correlated with the level of dysglycemia at diagnosis. In contrast, a coinhibitory signature, with an increased frequency of KLRG1+TIGIT+ CD27-CD8+ memory T cells, was observed in islet autoantibody-positive children who later progressed to T1D (stage 1). No alterations within CD27-CD8+ memory T cells were observed in adults with established T1D or in children during the initial seroconversion to islet autoantibody positivity. Single-cell multiomics analyses suggested that CD27-CD8+ T cells expressing the IFNG+TNF+ proinflammatory signature may be distinct from those expressing the KLRG1+TIGIT+ coinhibitory signature at the single-cell level. Collectively, our findings suggest that distinct blood CD8+ T-cell signatures could be employed as potential biomarkers of T1D progression.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Progresión de la Enfermedad
/
Linfocitos T CD8-positivos
/
Diabetes Mellitus Tipo 1
Idioma:
En
Revista:
Diabetes
Año:
2024
Tipo del documento:
Article