One amino acid difference is critical for suppression of the development of experimental autoimmune diabetes (EAD) with intravenous injection of insulinB:9-23 peptide.
InsulinB:9-23 peptide (insB:9-23) reactive T cells has been reported as crucial for type 1 diabetes. In this study, experimental autoimmune diabetes (EAD) mice, which subcutaneous immunization of ins1 or 2B:9-23 induced autoimmune diabetes in F1(B7.1B6 x BALB/c), was investigated for antigen specific therapy to delete pathogenic T cells. Intravenous injection of ins1 or 2B:9-23 significantly delayed the development of diabetes on the corresponding peptide-induced EAD (ins1EAD or ins2EAD) concomitant with reduced insulitis and insulin autoantibodies expression. Population of Foxp3(+) CD4(+) T cell was unchanged whereas the level of anti-insB:9-23 specific IgG(2a) but not IgG(1) were specifically decreased, suggesting reduction of pathogenic insB:9-23 reactive T cells. Most interestingly, intravenous administration of ins2B:9-23, whose amino acid sequence had one amino acid difference at position 9 delayed the development of diabetes in both ins1EAD and ins2EAD whereas ins1B:9-23 administration delayed diabetes in the ins1EAD but not ins2EAD, suggesting that one amino acid difference gives critical influence on the effect of intravenous injection of antigenic peptide for type 1 diabetes.
Okumachi
Yasuyo
Y
Department of Internal and Geriatric Medicine, Kobe University, Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Japan.
Moriyama
Hiroaki
H
Kameno
Mami
M
Arai
Takashi
T
Kishi
Minoru
M
Kurohara
Midori
M
Yamada
Katsumi
K
Yasuda
Hisafumi
H
Hara
Kenta
K
Yokono
Koichi
K
Nagata
Masao
M
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D051858:Forkhead Transcription Factors / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007165:Immunosuppression Therapy; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D011392:Proline / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D007328:Insulin; D010446:Peptide Fragments; C097877:insulin B (9-23); D012694:Serine; D011392:Proline