Single Insulin-Specific CD8+ T Cells Show Characteristic Gene Expression Profiles in Human Type 1 Diabetes
S Luce, F Lemonnier, JP Briand, J Coste, N Lahlou… - Diabetes, 2011 - Am Diabetes Assoc
Diabetes, 2011•Am Diabetes Assoc
OBJECTIVE 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. RESEARCH
DESIGN AND METHODS We used HLA-A* 02: 01 tetramers complexed to PPI peptides to …
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. RESEARCH
DESIGN AND METHODS We used HLA-A* 02: 01 tetramers complexed to PPI peptides to …
OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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.
RESULTS
Most autoreactive CD8+ T cells detected in recent-onset type 1 diabetic patients are specific for leader sequence peptides, notably PPI6–14, whereas CD8+ T cells in long-standing patients recognize the B-chain peptide PPI33–42 (B9–18). 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. PPI6–14–specific CD8+ T cells detected in one healthy control displayed Il-10 mRNA expression, which was not observed in diabetic patients.
CONCLUSIONS
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.
Am Diabetes Assoc