Inhalation of glutamic acid decarboxylase 65-derived peptides can protect against recurrent autoimmune but not alloimmune responses in the non-obese diabetic mouse.
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.
Ravanan
R
R
Department of Clinical Sciences at North Bristol, Bristol University, Bristol, UK. drrav@yahoo.com
Wong
S F
SF
Morgan
N G
NG
Mathieson
P W
PW
Smith
R M
RM
D000280:Administration, Inhalation; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D024201:Bystander Effect / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005968:Glutamate Decarboxylase / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis; D016381:Islets of Langerhans Transplantation; D007527:Isoenzymes / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000627:therapeutic use; D012008:Recurrence; D016019:Survival Analysis
D007527:Isoenzymes; D010446:Peptide Fragments; D016753:Interleukin-10; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2