Administration of a determinant of preproinsulin can induce regulatory T cells and suppress anti-islet autoimmunity in NOD mice

被引:7
作者
Arai, Takashi [1 ]
Moriyama, Hiroaki [1 ]
Shimizu, Mami [1 ]
Sasaki, Hirotomo [1 ]
Kishi, Minoru [1 ]
Okumachi, Yasuyo [1 ]
Yasuda, Hisafumi [1 ]
Hara, Kenta [1 ]
Yokono, Koichi [1 ]
Nagata, Masao [1 ]
机构
[1] Kobe Univ, Dept Internal & Geriatr Med, Grad Sch Med, Kobe, Hyogo 657, Japan
关键词
Diabetes; Immunotherapy; Insulin; Leader peptide; NOD; Regulatory T cell; NONOBESE DIABETIC MICE; ANTI-CD3; MONOCLONAL-ANTIBODY; INSULIN; ONSET; THERAPY; MOUSE; CYCLOSPORINE; AUTOANTIGEN; PREVENTION; PEPTIDES;
D O I
10.1016/j.clim.2010.02.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Antigen-specific immunotherapy is expected to be an ideal strategy for treating type 1 diabetes (T1D). We investigated the therapeutic efficacy of a peptide in the leader sequence of preproinsulin, which was selected because of its binding affinity to the MHC I-A(g7) molecule. Preproinsulin-1 L7-24 peptide (L7-24) emulsified in Freund's incomplete adjuvant was administered subcutaneously to NOD mice. Administration of L7-24 increased the proportion of regulatory T cells in the spleen. Splenocytes of NOD mice immunized with this peptide secreted IL-4 and IL-10 in response to L7-24. This peptide also significantly prevented the development of diabetes and cured some newly diabetic NOD mice without recurrence. L7-24 peptide, which has a high affinity for pockets of I-A(g7), induced regulatory T cells and showed therapeutic effects. This peptide may provide a new approach for developing antigen-specific immunotherapy for autoimmune diabetes. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:74 / 82
页数:9
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