Th2 dominance of T helper cell response to preproinsulin in individuals with preclinical type 1 diabetes

Ann N Y Acad Sci. 2002 Apr;958:209-13. doi: 10.1111/j.1749-6632.2002.tb02971.x.


In human type 1 diabetes (T1D) autoantibodies to insulin precede clinical disease, while little is known about the contribution of insulin-specific T lymphocytes-in particular, T helper (Th) subsets. Here we have studied the in vivo primed cytokine response to preproinsulin in peripheral blood mononuclear cells (PBMCs) and two major Th cell subsets-CD45RO+ memory cells and CD45RA+ naive/resting cells-in 35 individuals with HLA-DRB1*04, DQB1*0302 diabetes risk marker: 12 patients with T1D, 12 autoantibody-positive (Ab+) individuals, and 11 healthy controls. Cytokine secretion (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-10) was measured in the supernatants of the cultures stimulated with 21 overlapping preproinsulin peptides as well as proinsulin and insulin. In Ab+ individuals our results reveal higher IL-4 levels in CD45RO+ memory cells and higher IL-5 levels in CD45RA+ naive/resting cells, while higher IL-2 production was found in PBMCs. In contrast, in PBMCs of T1D patients higher IFN-gamma and IL-10 secretion was found. Our data delineate characteristic cytokine patterns in peripheral T lymphocytes from patients at different stages of the T1D development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • HLA Antigens / immunology
  • Humans
  • Immunologic Memory / immunology
  • Insulin
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Leukocyte Common Antigens / metabolism
  • Male
  • Middle Aged
  • Proinsulin / pharmacology*
  • Protein Precursors / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • HLA Antigens
  • Insulin
  • Interleukin-5
  • Protein Precursors
  • Interleukin-4
  • preproinsulin
  • Proinsulin
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1