GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients

Clin Immunol. 2011 Jan;138(1):117-26. doi: 10.1016/j.clim.2010.10.004. Epub 2010 Nov 1.

Abstract

Type 1 diabetes results from autoimmune destruction of insulin producing pancreatic β-cells. We have shown that treatment with alum-formulated glutamic acid decarboxylase 65 (GAD-alum) preserved residual insulin secretion and induced antigen-specific responses in children with recent onset type 1 diabetes. The aim of this study was to further investigate the immunomodulatory effect of GAD-alum, focusing on CD4(+)CD25(high) cells and their association to cytokine secretion. Samples obtained 21 and 30months after the initial injection of GAD-alum or placebo were included in the present study. GAD(65)-stimulation enhanced the percentage of CD4(+)CD25(high)FOXP3(+) cells, but reduced the percentage of CD4(+)CD25(+) cells, in samples from the GAD-alum treated group. Further, the GAD(65)-induced secretion of IL-5, -10, and -13 correlated with the expression of CD4(+)CD25(high)FOXP3(+) cells, but inversely with CD4(+)CD25(+) cells. These new data suggest that GAD-alum treatment induced GAD(65)-specific T cells with regulatory features.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alum Compounds* / administration & dosage
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Count
  • Child
  • Diabetes Mellitus, Type 1 / enzymology
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy*
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression / genetics
  • Gene Expression / immunology
  • Glutamate Decarboxylase / administration & dosage
  • Glutamate Decarboxylase / immunology*
  • Glutamate Decarboxylase / therapeutic use*
  • Humans
  • Immunosuppression / methods
  • Interferon-gamma / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Interleukins / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Transforming Growth Factor beta / genetics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Alum Compounds
  • Autoantibodies
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • aluminum sulfate
  • Interferon-gamma
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2