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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 &lt; 0.05), their non-diabetic siblings a reduced CD4+ T-helper cell count (p &lt; 0.05), and their parents a reduced percentage and number of CD3+ T cells (p &lt; 0.01 and p &lt; 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 &lt; 0.01, p &lt; 0.05 and p &lt; 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 &lt; 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.

diabetologia

Lymphocyte subset abnormalities, autoantibodies and their relationship with HLA DR types in children with Type 1 (insulin-dependent) diabetes and their first degree relatives