title: Lymphocyte subset abnormalities, autoantibodies and their relationship with HLA DR types in children with type 1 (insulin-dependent) diabetes and their first degree relatives.
abstract: Type 1 (insulin-dependent) diabetes mellitus is associated with abnormalities of circulating lymphocyte subsets and autoantibodies. To investigate the prevalence of these in non-diabetic siblings and non-diabetic patients of children with Type 1 diabetes, we analysed T-cell subsets of function and activation in 31 families with an index case of Type 1 diabetes and related these to autoantibodies and HLA DR type. Using two and three colour cytofluorimetry, we studied total and activated (HLA-DR+) CD3+, CD4+, CD8+, lymphocytes and on CD4+ lymphocytes the CD45RA/RO "naive" and "memory" cell phenotypes. Diabetic children (mean duration of disease 3.1 years) had a reduced total lymphocyte count (p < 0.05), their non-diabetic siblings a reduced CD4+ T-helper cell count (p < 0.05), and their parents a reduced percentage and number of CD3+ T cells (p < 0.01 and p < 0.05) compared with age-matched control subjects. Diabetic children, their siblings and parents all had significantly increased levels of activated CD4+ T-helper cells (p < 0.01, p < 0.05 and p < 0.01). In diabetic children and their siblings there was a significant over-expression of the CD45RO "memory" cell marker and significant under-expression of the CD45RA "naive" cell marker, whilst these were normal in the parents. Islet cell antibody positive diabetic children had significantly higher levels of CD45RO-expressing CD4+ lymphocytes than those who were islet cell antibody negative (p < 0.05). Amongst the siblings and parents, possession of HLA-DR4 was associated with lower percentages of CD4+ and higher percentages of CD8+ T cells. These findings extend current knowledge about the role of immunoregulatory CD45RA/RO cells in Type 1 diabetes. In addition, they demonstrate lymphocyte subset abnormalities in unaffected family members, some of which may be influenced by HLA DR alleles.
authors.affiliation: Department of Immunology, King's College School of Medicine and Dentistry, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Peakman
authors.forename: T
authors.initials: T
authors.lastname: Warnock
authors.forename: A
authors.initials: A
authors.lastname: Vats
authors.forename: G L
authors.initials: GL
authors.lastname: McNab
authors.forename: J
authors.initials: J
authors.lastname: Underhill
authors.forename: P T
authors.initials: PT
authors.lastname: Donaldson
authors.forename: D
authors.initials: D
authors.lastname: Vergani
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D017252:CD3 Complex / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D016827:CD8 Antigens / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D009679:Nuclear Family; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens