Vaccination with glutamic acid decarboxylase plasmid DNA protects mice from spontaneous autoimmune diabetes and B7/CD28 costimulation circumvents that protection.
The nonobese diabetic (NOD) mouse develops spontaneous T-cell-dependent autoimmune diabetes. We tested here whether vaccination of NOD mice with a plasmid DNA encoding glutamic acid decarboxylase (GAD), an initial target islet antigen of autoimmune T cell repertoire, would modulate their diabetes. Our results showed that vaccination of young or old female NOD mice with the GAD-plasmid DNA, but not control-plasmid DNA, effectively prevented their diabetes, demonstrating that GAD-plasmid DNA vaccination is quite effective in abrogating diabetes even after the development of insulitis. The prevention of diabetes did not follow the induction of immunoregulatory Th2 cells but was dependent upon CD28/B7 costimulation. Our results suggest a potential for treating spontaneous autoimmune diabetes via DNA vaccination with plasmids encoding self-Ag.
Balasa
B
B
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Boehm
B O
BO
Fortnagel
A
A
Karges
W
W
Van Gunst
K
K
Jung
N
N
Camacho
S A
SA
Webb
S R
SR
Sarvetnick
N
N
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D005968:Glutamate Decarboxylase