title: Administration of a determinant of preproinsulin can induce regulatory T cells and suppress anti-islet autoimmunity in NOD mice.
abstract: 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.
authors.affiliation: Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Mami
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Sasaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Kishi
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Okumachi
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Kenta
authors.initials: K
authors.lastname: Hara
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokono
authors.forename: Masao
authors.initials: M
authors.lastname: Nagata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001786:Blood Glucose / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D003208:Concanavalin A / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D016233:Immunotherapy, Active / Q000379:methods*; D007328:Insulin / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014611:Vaccination
chemical_list: D001786:Blood Glucose; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; C013737:preproinsulin; D007371:Interferon-gamma