Different CD8+ T-Cell Targets in New Established Diabetes

Autoreactive CD8+ T cells specific for preproinsulin target different epitopes

WEDNESDAY, Oct. 19 (HealthDay News) -- Autoreactive CD8+ T cells specific for preproinsulin (PPI) include central and effector memory cells and show different specificities for epitopes in patients with recent-onset and long-standing type 1 diabetes (T1D), according to a study published online Oct. 13 in Diabetes.

Sandrine Luce, from the Institut National de la Santé et de la Recherche Médicale U986 in Paris, and colleagues characterized HLA class I-restricted autoreactive CD8+ T cells specific for PPI in patients with recent-onset and long-standing T1D and healthy controls. Circulating PPI-specific CD8+ T cells were enumerated using HLA-A *02:01 tetramers complexed to PPI peptides and characterized using membrane markers and single-cell polymerase chain reaction.

The investigators found that most CD8+ T cells detected in patients with recent-onset T1D were specific for leader sequence peptides PPI6-14; and in patients with long-standing T1D, they were specific for B-chain peptide PPI33-42. Both CD8+ T-cells specificities were found to be mainly naive, central, and effector memory cells with gene-expression profile distinct from cytomegalovirus-specific CD8+ T cells. One of the healthy controls displayed Il-10 mRNA expression in PPI6 to 14-specific CD8+ T cells, which was absent in patients with diabetes.

"PPI-specific CD8+ T cells in type 1 diabetic patients include central memory and target different epitopes in new-onset versus long-standing disease," the authors write.

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