title: Analyses of regulatory CD4+ CD25+ FOXP3+ T cells and observations from peripheral T cell subpopulation markers during the development of type 1 diabetes in children.
abstract: Our aim was to study whether the aberrant amount or function of regulatory T cells is related to the development of type 1 diabetes (T1D) in children. We also set out to investigate the balance of different T cell subtype markers during the T1D autoimmune process. Treg cells were quantified with flow cytometric assay, and the suppression capacity was analysed with a carboxyfluorescein succinimidyl ester (CFSE)-based T cell suppression assay in children in various phases of T1D disease process and in healthy autoantibody-negative control children. The mRNA expression of different T cell subpopulation markers was analysed with real-time qPCR method. The proportion and suppression capacity of regulatory T cells were similar in seroconverted children at an early stage of beta cell autoimmunity and also in children with T1D when compared to healthy and autoantibody-negative children. Significant differences were observed in the mRNA expression of different T cell subpopulation markers in prediabetic children with multiple (≥ 2) autoantibodies and in children with newly diagnosed T1D when compared to the control children. In conclusion, there were no quantitative or functional differences in regulatory T cells between the case and control groups in any phase of the autoimmune process. Decreased mRNA expression levels of T cell subtype markers were observed in children with multiple islet autoantibodies and in those with newly diagnosed T1D, probably reflecting an exhaustion of the immune system after the strong immune activation during the autoimmune process or a generally aberrant immune response related to the progression of the disease.
authors.affiliation: Department of Pediatrics, Medical Research Center Oulu, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.|Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Hamari
authors.affiliation: Department of Pediatrics, Medical Research Center Oulu, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.|Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kirveskoski
authors.affiliation: Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Glumoff
authors.affiliation: Department of Pediatrics, Medical Research Center Oulu, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.|Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Kulmala
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Simell
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Folkhälsan Research Center, Helsinki, Finland.|Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Knip
authors.affiliation: Department of Pediatrics, Medical Research Center Oulu, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Veijola
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D011236:Prediabetic State / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger