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Lymphocyte subsets and activation in prediabetes.

C L Hitchcock, W J Riley, A Alamo

    Diabetes
    |December 1, 1986
    PubMed
    Summary
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    In prediabetic and insulin-dependent diabetes mellitus (IDDM) patients, increased HLA-DR antigen density on T-lymphocytes correlated with islet cell autoantibodies and impaired insulin release. These findings suggest T-lymphocyte activation in early diabetes.

    Area of Science:

    • Immunology
    • Endocrinology
    • Diabetes Research

    Background:

    • Type 1 diabetes, or insulin-dependent diabetes mellitus (IDDM), is an autoimmune disease characterized by the destruction of pancreatic beta cells.
    • Islet cell autoantibodies (ICA) are markers of the prediabetic phase, indicating autoimmune activity against the islets.
    • Understanding lymphocyte behavior in early diabetes is crucial for developing preventative or therapeutic strategies.

    Purpose of the Study:

    • To investigate lymphocyte abnormalities and activation markers in individuals with varying stages of IDDM development.
    • To assess the expression and density of HLA-DR antigens on T-lymphocyte subsets in relation to autoantibodies and glucose metabolism.

    Main Methods:

    • Dual fluorescence flow cytometry was used to analyze peripheral blood lymphocytes from 65 individuals.

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  • Participants included prediabetic patients (ICA+), newly diagnosed IDDM patients, ICA-negative relatives, and ICA-negative controls.
  • Analysis focused on B cells, T-lymphocyte subsets (Th, Tc/s), interleukin 2 receptor expression, and HLA-DR antigen expression and density.

    • Main Results:

    • No significant differences in B cell, T-lymphocyte subset percentages, or interleukin 2 receptor expression were observed among groups.
    • Increased numbers of HLA-DR expressing T-lymphocytes were found in a subset of patients.
    • Significantly increased relative density of DR antigen (RAD-DR) on both helper T-lymphocytes (Th) and cytotoxic/suppressor T-lymphocytes (Tc/s) was observed in 13 of 38 patients.
    • RAD-DR on Tc/s correlated with ICA titer and was highest in DR3/4-phenotyped T-lymphocytes.
    • Increased RAD-DR was also found in patients with impaired insulin release responses.

    Conclusions:

    • While lymphocyte subset percentages and IL-2 receptor expression were not altered, increased HLA-DR antigen density on T-lymphocytes is a key finding in prediabetic and early IDDM stages.
    • This increased antigen density correlates with the presence of islet cell autoantibodies and impaired insulin secretion, suggesting T-lymphocyte activation.
    • These findings highlight the role of T-lymphocyte activation in the pathogenesis of IDDM and may serve as potential biomarkers.