title: Combined insulin B:9-23 self-peptide and polyinosinic-polycytidylic acid accelerate insulitis but inhibit development of diabetes by increasing the proportion of CD4+Foxp3+ regulatory T cells in the islets in non-obese diabetic mice.
abstract: Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes. Combined treatment with B:9-23 peptide and polyinosinic-polycytidylic acid (poly I:C), but neither alone, induce insulitis in normal BALB/c mice. In contrast, the combined treatment accelerated insulitis, but prevented diabetes in NOD mice. Our immunofluorescence study with anti-CD4/anti-Foxp3 revealed that the proportion of Foxp3 positive CD4(+)CD25(+) regulatory T cells (Tregs) was elevated in the islets of NOD mice treated with B:9-23 peptide and poly I:C, as compared to non-treated mice. Depletion of Tregs by anti-CD25 antibody hastened spontaneous development of diabetes in non-treated NOD mice, and abolished the protective effect of the combined treatment and conversely accelerated the onset of diabetes in the treated mice. These results indicate that poly I:C combined with B:9-23 peptide promotes infiltration of both pathogenic T cells and predominantly Tregs into the islets, thereby inhibiting progression from insulitis to overt diabetes in NOD mice.
authors.affiliation: Department of Endocrinology and Metabolism, Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Fukushima
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Satoh
authors.forename: Mami
authors.initials: M
authors.lastname: Nakahara
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.forename: Koji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Edwin
authors.initials: E
authors.lastname: Liu
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage*; D011070:Poly I-C / Q000008:administration & dosage*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007328:Insulin; D010446:Peptide Fragments; C097877:insulin B (9-23); D011070:Poly I-C