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Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease

Tsunekazu Oikawa, Yosuke Kamimura, Hisaya Akiba, Hideo Yagita, Ko Okumura, Hiroki Takahashi, Mikio Zeniya, Hisao Tajiri and Miyuki Azuma
J Immunol October 1, 2006, 177 (7) 4281-4287; DOI: https://doi.org/10.4049/jimmunol.177.7.4281
Tsunekazu Oikawa
*Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;
†Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University Medical School, Tokyo, Japan; and
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Yosuke Kamimura
*Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;
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Hisaya Akiba
‡Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
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Hideo Yagita
‡Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
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Ko Okumura
‡Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
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Hiroki Takahashi
†Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University Medical School, Tokyo, Japan; and
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Mikio Zeniya
†Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University Medical School, Tokyo, Japan; and
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Hisao Tajiri
†Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University Medical School, Tokyo, Japan; and
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Miyuki Azuma
*Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;
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Abstract

Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses. We examined Tim-3 and its ligand expression as well as the effects of anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease (aGVHD). In mice with aGVHD, Tim-3 expression was markedly up-regulated on splenic and hepatic CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages, and this was especially dramatic in hepatic CD8+ T cells. Both donor- and host-derived CD8+ T cells induced similar levels of Tim-3. Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes. The administration of anti-Tim-3 mAbs accelerated aGVHD, as demonstrated by body weight loss, reduction in total splenocyte number, and infiltration of lymphocytes in the liver. IFN-γ expression by splenic and hepatic CD4+ and CD8+ T cells was significantly augmented by anti-Tim-3 mAb treatment. In addition, the cytotoxicity against host alloantigen by donor CD8+ T cells was enhanced. These results demonstrate that the anti-Tim-3 treatment in aGVHD augmented the activation of effector T cells expressing IFN-γ or exerting cytotoxicity. Our results suggest that Tim-3 may play a crucial role in the regulation of CD8+ T cells responsible for the maintenance of hepatic homeostasis and tolerance.

  • Received February 17, 2006.
  • Accepted June 14, 2006.
  • Copyright © 2006 by The American Association of Immunologists
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The Journal of Immunology: 177 (7)
The Journal of Immunology
Vol. 177, Issue 7
1 Oct 2006
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Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease
Tsunekazu Oikawa, Yosuke Kamimura, Hisaya Akiba, Hideo Yagita, Ko Okumura, Hiroki Takahashi, Mikio Zeniya, Hisao Tajiri, Miyuki Azuma
The Journal of Immunology October 1, 2006, 177 (7) 4281-4287; DOI: 10.4049/jimmunol.177.7.4281

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Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease
Tsunekazu Oikawa, Yosuke Kamimura, Hisaya Akiba, Hideo Yagita, Ko Okumura, Hiroki Takahashi, Mikio Zeniya, Hisao Tajiri, Miyuki Azuma
The Journal of Immunology October 1, 2006, 177 (7) 4281-4287; DOI: 10.4049/jimmunol.177.7.4281
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