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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, CD8-Positive T-Lymphocytes, Cells, Cultured, Diabetes Mellitus, Type 1, Female, Gene Expression Profiling, Humans, Insulin, Male, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction.
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Do single insulin-specific CD8+ T cells show characteristic gene expression profiles in human type 1 diabetes? Context: Both the early steps and the high recurrence of autoimmunity once the disease is established are unexplained in human type 1 diabetes. Because CD8(+) T cells are central and insulin is a key autoantigen in the disease process, our objective was to characterize HLA class I-restricted autoreactive CD8(+) T cells specific for preproinsulin (PPI) in recent-onset and long-standing type 1 diabetic patients and healthy control subjects. We used HLA-A*02:01 tetramers complexed to PPI peptides to enumerate circulating PPI-specific CD8(+) T cells in patients and characterize them using membrane markers and single-cell PCR. Most autoreactive CD8(+) T cells detected in recent-onset type 1 diabetic patients are specific for leader sequence peptides, notably PPI(6-14), whereas CD8(+) T cells in long-standing patients recognize the B-chain peptide PPI(33-42) (B(9-18)). Both CD8(+) T-cell specificities are predominantly naïve, central, and effector memory cells, and their gene expression profile differs from cytomegalovirus-specific CD8(+) T cells. PPI(6-14)-specific CD8(+) T cells detected in one healthy control displayed Il-10 mRNA expression, which was not observed in diabetic patients.
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PPI-specific CD8(+) T cells in type 1 diabetic patients include central memory and target different epitopes in new-onset versus long-standing disease. Our data support the hypothesis that insulin therapy may contribute to the expansion of autoreactive CD8(+) T cells in the long term. Final Decision: yes