title: Single insulin-specific CD8+ T cells show characteristic gene expression profiles in human type 1 diabetes.
abstract: 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.
  
  
  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 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.
  
  
  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.
authors: INSERM, U986, Paris, France.
authors: Sandrine
authors: S
authors: Luce
authors: François
authors: F
authors: Lemonnier
authors: Jean-Paul
authors: JP
authors: Briand
authors: Joel
authors: J
authors: Coste
authors: Najiba
authors: N
authors: Lahlou
authors: Sylviane
authors: S
authors: Muller
authors: Etienne
authors: E
authors: Larger
authors: Benedita
authors: B
authors: Rocha
authors: Roberto
authors: R
authors: Mallone
authors: Christian
authors: C
authors: Boitard
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin