[Antigen specific treatment for the inhibition and remission of type 1 diabetes].
Treatment with anti-CD3 antibodies appears promising to preserve residual beta-cell function in recent onset type 1 diabetes although many patients had therapy related adverse events. Insulin is an important islet antigen and autoimmunity to insulin may be central to disease pathogenesis of type 1 diabetes in man and NOD mouse. Evidence is strongest for the NOD mouse model, where blocking immune responses to insulin by amino acid substitution at positions B: 16, prevents diabetes. Insulin can be used to immunologically prevent diabetes of NOD mice, however, insulin-based preventive immunoregulation of diabetes in man is not yet possible. Treatment of NOD mice with insulin B-chain peptide and poly I: C, a Toll-like receptor 3 ligand, induces the pathogenic T cells as well as regulatory T cells and recruits them into the islets. Intranasal treatment with insulin B-chain analogue peptide with amino acid substitutions at positions B: 16 and 19 prevented the progression to diabetes and induced remission from hyperglycemia when co-administered with a mucosal adjuvant cholera toxin. Thus, an antigenic peptide vaccination with an alternative adjuvant or route might induce antigen-specific regulatory cell populations rather than pathogenic T cells. We believe that such an improved antigen specific therapy could provide more efficient and safer disease suppression and remission for human type 1 diabetes.
Abiru
Norio
N
Department of Endocrinology and Metabolism, Nagasaki University Hospital of Medicine and Dentistry.
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control* / Q000628:therapy; D007328:Insulin / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000276:immunology*; D011070:Poly I-C / Q000008:administration & dosage
D007328:Insulin; D007519:Isoantigens; D010446:Peptide Fragments; C097877:insulin B (9-23); D011070:Poly I-C