title: Immune regulatory T cells in siblings of children suffering from type 1 diabetes mellitus.
abstract: Patients with type 1 diabetes are suffering from defects in immune regulatory cells. Their siblings may be at increased risk of type 1 diabetes especially if they are carriers of certain human leucocyte antigen (HLA) alleles. In a prospective non-randomized study, we intended to evaluate 31 healthy siblings of paediatric patients with type 1 diabetes and explore immune regulatory populations of CD4+CD25+ T cells and natural killer (NK) T cells. Tested siblings of type 1 diabetes patients were stratified according to the HLA-associated risk of possible diabetes development. Immune regulatory function of CD4+CD25+ T cells was tested in vitro. Significant differences in CD4+CD25+ but not in NK T cells have been identified. Siblings of type 1 diabetes patients carrying high risk HLA alleles (DQA1*05, DQB1*0201, DQB1*0302) had significantly lower number of immune regulatory CD4+CD25+ T cells than the age-matched healthy controls or siblings carrying low-risk HLA alleles (DQB1*0301, DQB1*0603, DQB1*0602). Regulatory function of CD4+CD25+ T cells demonstrated a dose-escalation effect. In siblings of type 1 diabetes patients, the defect in immune regulatory CD4+CD25+ T cells exists in association with genetic HLA-linked risk for type 1 diabetes.
authors.affiliation: 1st Department of Pediatrics, Masaryk University, Brno, Czech Republic. jmichalek@fnbrno.cz
authors.forename: J
authors.initials: J
authors.lastname: Michalek
authors.forename: Z
authors.initials: Z
authors.lastname: Vrabelova
authors.forename: Z
authors.initials: Z
authors.lastname: Hrotekova
authors.forename: M
authors.initials: M
authors.lastname: Kyr
authors.forename: M
authors.initials: M
authors.lastname: Pejchlova
authors.forename: S
authors.initials: S
authors.lastname: Kolouskova
authors.forename: M
authors.initials: M
authors.lastname: Faresjö
authors.forename: K
authors.initials: K
authors.lastname: Stechova
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000502:physiology; D008297:Male; D035781:Siblings; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens