@article{oai:nagasaki-u.repo.nii.ac.jp:00014099,
 author = {阿比留, 教生},
 issue = {6},
 journal = {日本臨床免疫学会会誌, Japanese Journal of Clinical Immunology},
 month = {Dec},
 note = {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., 日本臨床免疫学会会誌, 31(6), pp.432-439; 2008},
 pages = {432--439},
 title = {1型糖尿病の発症阻止と寛解誘導},
 volume = {31},
 year = {2008}
}