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.
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| 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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| Authors | Keiko Fukushima, Norio Abiru, Yuji Nagayama, Masakazu Kobayashi, Tsuyoshi Satoh, Mami Nakahara, Eiji Kawasaki, Hironori Yamasaki, Satoshi Ueha, Koji Matsushima, Edwin Liu, Katsumi Eguchi |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 367 Issue 4 Pg. 719-24 (Mar 21 2008) ISSN: 1090-2104 [Electronic] United States |
| PMID | 18194666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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