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Thymic dysfunction in the mutant diabetic (db/db) mouse.

M Dardenne, W Savino, L N Gastinel

    Journal of Immunology (Baltimore, Md. : 1950)
    |March 1, 1983
    PubMed
    Summary
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    Diabetic mice exhibit accelerated thymus aging and reduced serum thymic factor (FTS). These mice also develop FTS-inhibiting immunoglobulins, suggesting thymus dysfunction contributes to autoimmune disease in diabetes.

    Area of Science:

    • Immunology
    • Endocrinology
    • Mouse Models

    Background:

    • Thymic function is crucial for immune system development.
    • Genetic diabetes (db/db mice) is associated with autoimmune manifestations.
    • Age-dependent decline in thymic function is a known phenomenon.

    Purpose of the Study:

    • To investigate thymic function in genetically diabetic (db/db) mice.
    • To assess serum thymic factor (FTS) levels and identify potential inhibitors.
    • To analyze histological and ultrastructural changes in the thymus of diabetic mice.

    Main Methods:

    • Serum thymic factor (FTS) levels were measured using a rosette assay.
    • Inhibitory molecules in sera were detected in vitro and in vivo.
    • Thymus histology and ultrastructure were examined.

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  • Indirect immunofluorescence was used to quantify FTS-positive cells.

    • Main Results:

    • Diabetic mice showed an accelerated age-dependent decline in FTS levels compared to controls.
    • FTS-inhibiting immunoglobulins were detected in the sera of diabetic mice.
    • Histological analysis revealed accelerated thymic involution, including lymphocytic depletion and increased Hassall's corpuscles.
    • Ultrastructural studies showed cytoplasmic vacuoles in thymic epithelial cells.
    • Diabetic mice had significantly fewer FTS-positive cells in their thymuses.

    Conclusions:

    • Diabetic mice exhibit significant thymic abnormalities, including reduced FTS levels and impaired thymic function.
    • The presence of FTS-inhibiting immunoglobulins suggests an autoimmune component affecting the thymus.
    • These thymic dysfunctions may contribute to the pathogenesis of autoimmune disease in db/db mice.