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Diabetes 54:1407-1414, 2005
© 2005 by the American Diabetes Association, Inc.

Functional Defects and the Influence of Age on the Frequency of CD4+CD25+ T-Cells in Type 1 Diabetes

Todd M. Brusko1, Clive H. Wasserfall1, Michael J. Clare-Salzler1, Desmond A. Schatz2, and Mark A. Atkinson1

1 Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida
2 Department of Pediatrics, University of Florida, Gainesville, Florida

CD4+CD25+ T-cells appear to play a crucial role in regulating the immune response. Therefore, we evaluated the peripheral blood frequency and function of CD4+CD25+ T-cells in 70 type 1 diabetic patients and 37 healthy individuals. Interestingly, a positive correlation was observed between increasing age and CD4+CD25+ T-cell frequency in both subject groups. In contrast to previous studies of nonobese diabetic mice and type 1 diabetic patients, similar frequencies of CD4+CD25+ and CD4+CD25+Bright T-cells were observed in healthy control subjects and type 1 diabetic patients of similar age. There was no difference between type 1 diabetic subjects of recent-onset versus those with established disease in terms of their CD4+CD25+ or CD4+CD25+BrightT-cell frequency. However, type 1 diabetic patients were markedly defective in their ability to suppress the proliferation of autologous effector T-cells in vitro. This type 1 diabetes-associated defect in suppression was associated with reduced production of interleukin (IL)-2, {gamma}-interferon, and transforming growth factor-ß, whereas other cytokines including those of adaptive and innate immunity (IL-10, IL-1ß, IL-6, IL-8, IL-12p70, and tumor necrosis factor-{alpha}) were similar in control subjects and type 1 diabetic patients. These data suggest that age strongly influences the frequency of CD4+CD25+ T-cells and that function, rather than frequency, may represent the means by which these cells associate with type 1 diabetes in humans.


Address correspondence and reprint requests to Mark A. Atkinson, PhD, Department of Pathology, College of Medicine, University of Florida, ARB-R3-128, 1600 SW Archer Rd., Gainesville, FL 32610-0275. E-mail: atkinson{at}ufl.edu

Abbreviations: APC, allophycocyanin; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-{gamma}, {gamma}-interferon; IL, interleukin; PE, phycoerythrin; Teff, CD4+CD25 effector T-cell; TGF, transforming growth factor; TNF, tumor necrosis factor; Treg, CD4+CD25+ regulatory T-cell


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