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

Biochemical and Biophysical Research Communications
Keiko FukushimaKatsumi Eguchi

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.

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Citations

Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Li ZhangGeorge S Eisenbarth
Nov 10, 2011·Diabetes/metabolism Research and Reviews·Li ZhangGeorge S Eisenbarth
May 22, 2013·Journal of Diabetes Research·Cathleen PetzoldKarsten Kretschmer
May 26, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathaniel J SchuldtBryce A Binstadt
Jan 6, 2009·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Norio Abiru
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Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Subha Karumuthil-MelethilChenthamarakshan Vasu
Aug 22, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Subha Karumuthil-MelethilChenthamarakshan Vasu
Jul 3, 2008·Current Opinion in Endocrinology, Diabetes, and Obesity

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