CD4+ T Cell Proliferation in Response to GAD and Proinsulin in Healthy, Pre-Diabetic, and Diabetic Donors

Ann N Y Acad Sci. 2004 Dec;1037:16-21. doi: 10.1196/annals.1337.003.


The ability to measure proliferation of autoantigen-specific T cells is critical for the evaluation of cellular immune function. Using a novel, sensitive, CFSE-based assay, we were able to directly quantitate autoantigen-specific CD4(+) T cell proliferation. However, peripheral blood cells from healthy, pre-diabetic and diabetic donors exhibited overlap in responses to glutamic acid decarboxylase (GAD65) and proinsulin (PI). This indicates that autoantigen-induced CD4(+) T cell proliferation in a functionally complex cell population may not discriminate disease in the general population. Clear discrimination was found between diabetic and healthy sibs, suggesting the need to standardize the genetic and environmental background. In addition, the ability of the CFSE assay to allow analysis of the phenotype and function of autoantigen-responsive T cells may improve discrimination.

Publication types

  • Comparative Study

MeSH terms

  • Blood Donors*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / immunology*
  • Flow Cytometry
  • Fluoresceins / metabolism
  • Fluorescent Dyes / metabolism
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mitotic Index
  • Prediabetic State / immunology*
  • Proinsulin / immunology*
  • Recombinant Proteins / metabolism
  • Sensitivity and Specificity
  • Succinimides / metabolism
  • Tetanus Toxoid / immunology
  • Time Factors


  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Fluoresceins
  • Fluorescent Dyes
  • Recombinant Proteins
  • Succinimides
  • Tetanus Toxoid
  • Proinsulin
  • Glutamate Decarboxylase