Inhalation of glutamic acid decarboxylase 65-derived peptides can protect against recurrent autoimmune but not alloimmune responses in the non-obese diabetic mouse

Clin Exp Immunol. 2007 May;148(2):368-72. doi: 10.1111/j.1365-2249.2007.03358.x.

Abstract

Systemic administration of islet-derived antigens has been shown to protect against diabetes in the non-obese diabetic (NOD) mouse by the induction of antigen-specific regulatory T cells. Bystander regulation to related and unrelated islet-derived antigens (intramolecular and intermolecular recognition) in this context is recognized. We tested if intranasal administration of glutamic acid decarboxylase 65 (GAD 65)-derived peptides could protect against both autoimmune and, through bystander regulation, alloimmune responses in a NOD mouse model. Spontaneously diabetic female NOD mice underwent islet transplantation from either C57Bl/6 or NOD islet donors. Islet recipients were treated with intranasal GAD 65-derived peptides or control (ovalbumin) peptide pre- and post-transplantation. In-vitro analysis of the effect of inhalation was defined using lymph node proliferation assays and supernatant analysis for cytokines. GAD 65-derived peptide inhalation resulted in significant protection against recurrent autoimmune disease, with the generation of an interleukin (IL)-10-producing immune phenotype in a syngeneic islet transplant model. This phenotype, however, was not robust enough to protect against alloimmune responses. Inhalation of GAD-derived peptides induces an immunoregulatory response that protects against recurrent autoimmune, but not alloimmune responses in the NOD mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / prevention & control*
  • Bystander Effect / drug effects
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Female
  • Glutamate Decarboxylase / therapeutic use*
  • Interleukin-10 / biosynthesis
  • Islets of Langerhans Transplantation
  • Isoenzymes / therapeutic use*
  • Mice
  • Mice, Inbred NOD
  • Peptide Fragments / therapeutic use
  • Recurrence
  • Survival Analysis

Substances

  • Isoenzymes
  • Peptide Fragments
  • Interleukin-10
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2