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1型糖尿病の発症阻止と寛解誘導


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Title: 1型糖尿病の発症阻止と寛解誘導
Other Titles: Antigen specific treatment for the inhibition and remission of type 1 diabetes
Authors: 阿比留, 教生
Authors (alternative): Abiru, Norio
Issue Date: 31-Dec-2008
Publisher: 日本臨床免疫学会 / The Japan Society for Clinical Immunology
Citation: 日本臨床免疫学会会誌, 31(6), pp.432-439; 2008
Abstract: 近年,抗CD3抗体などの生物学的製剤を中心に,ヒト1型糖尿病の分野においても,疾患の治癒・寛解を目指し治療法の開発研究がすすめられているが,安全性,経済性などの問題を抱えている.インスリンは,ヒト,NODマウスの1型糖尿病発症に関連した主要自己抗原である.膵島浸潤T細胞に反応せず,しかも,血糖降下作用を維持する変異インスリン(B鎖16位残基アラニン置換)のみを発現するNODマウスでは,インスリン自己抗体が発現せず,糖尿病も発症しない.NODマウスに,poly I:Cをアジュバントに,インスリンB鎖ペプチドを皮下投与すると,制御性T細胞だけでなく,攻撃側のeffector細胞も膵島内に誘導する.一方,インスリンB鎖16, 19位残基を置換したアナログペプチドを,コレラトキシンをアジュバントに経鼻投与すると,強力な糖尿病発症の抑制と高血糖からの寛解を誘導した.このように,膵島抗原を用いた免疫学的治療法は,投与ルートやアジュバント,補助療法に改良を加え,制御性T細胞を優位に誘導することより,今後,ヒト1型糖尿病において,安全な発症阻止,寛解誘導の治療法となる可能性がある. / 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.
Keywords: type 1 diabetes / prevention / autoantigen / insulin peptide / regulatory T cells
URI: http://hdl.handle.net/10069/24074
ISSN: 09114300
DOI: 10.2177/jsci.31.432
Rights: Copyright (c) 2008 日本臨床免疫学会
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/24074

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