title: Diminished Th1-like response to autoantigens in children with a high risk of developing type 1 diabetes.
abstract: The exact role of T-helper (Th) cells that precede the clinical manifestation of type 1 diabetes remains unclear. The aim of this investigation was to study the Th1- and Th2-like profile in children and adults with high risk of developing the disease. Peripheral blood mononuclear cells were collected from high-risk children and adults and from healthy individuals matched for age and gender. Using the sensitive enzyme-linked immunospot (ELISPOT) technique to divide Th1- from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 was analysed from lymphocytes spontaneously and after in vitro stimulation with different antigens, based on present paradigms regarding the pathogenesis of type 1 diabetes. Compared to the response observed in healthy individuals, we found that individuals with a high risk of developing type 1 diabetes, especially children, responded with less IFN-gamma secretion to the three autoantigens glutamic acid decarboxylase 65 (GAD65), insulin and tyrosinphosphatase (IA-2). Thus, a diminished Th1-like response by in vitro autoantigen stimulation was observed in especially children with a high risk of developing type 1 diabetes. Reduced Th1/Th2 response was related to signs of beta cell exhaustion.
authors.affiliation: Division of Paediatrics and Diabetes Research Centre, Department of Molecular & Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. maria.faresjo@imk.liu.se
authors.forename: M G E
authors.initials: MG
authors.lastname: Karlsson Faresjö
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
mesh_terms: D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000494:pharmacology; D011236:Prediabetic State / Q000201:enzymology / Q000276:immunology*; D011384:Proinsulin / Q000097:blood; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D001324:Autoantigens; D007328:Insulin; D015847:Interleukin-4; D009536:Niacinamide; D007371:Interferon-gamma; D002097:C-Reactive Protein; D011384:Proinsulin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase