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Proceedings of the National Academy of Sciences of the United States of America >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/2241/107528
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| Title: | Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice |
| Authors: | Nabekura, Tsukasa
Shibuya, Kazuko
Takenaka, Eri
Kai, Hirayasu
Shibata, Kai
Yamashita, Yumi
Harada, Kyoichi
Tahara-Hanaoka, Satoko
Honda, Shin-ichiro
Shibuya, Akira
渋谷, 和子
甲斐, 平康
田原, 聡子
本多, 伸一郎
渋谷, 彰 |
| Issue Date: | Oct-2010 |
| Publisher: | National Academy of Sciences |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States o f America |
| Volume: | 107 |
| Issue: | 43 |
| Start Page: | 18593 |
| End Page: | 18598 |
| DOI: | 10.1073/pnas.1005582107 |
| PMID: | 20937876 |
| Abstract: | Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those that received allogeneic WT splenocytes. Donor CD8+ T cells deficient in DNAM-1 showed significantly less proliferation and infiltration of the liver and intestines of recipient mice and produced less IFN-γ after coculture with allogeneic splenocytes than WT CD8+ T cells. Mice prophylactically treated with an anti–DNAM-1 antibody showed milder GVHD and lower mortality than those treated with a control antibody. Moreover, treatment with a single administration of the antibody after the overt onset of GVHD ameliorated GVHD and prolonged survival. Finally, we show that the anti–DNAM-1 antibody therapy also ameliorated the overt GVHD in lethally irradiated mice after MHC-matched, minor antigen-mismatched bone marrow transplantation. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD. |
| URI: | http://hdl.handle.net/2241/107528 |
| Rights: | ©2010 by the National Academy of Sciences |
| Text Version: | author |
| Appears in Collections: | 渋谷 和子 (Shibuya Kazuko)
甲斐 平康 (Kai Hirayasu)
田原 聡子 (Tahara Satoko)
本多 伸一郎 (Honda Shin-ichiro)
渋谷 彰 (Shibuya Akira)
Proceedings of the National Academy of Sciences of the United States of America
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