Blockade of the 4-1BB Pathway Attenuates Graft Arterial Disease in Cardiac Allografts

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概要

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• 4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, binds the 4-1BB ligand (4-1BBL) and works as a costimulatory molecule and regulates T cell-mediated immune responses. Because T cell-mediated immunity is associated with graft arterial disease (GAD), we investigated the role of the 4-1BB pathway in the progression of GAD.<br> Hearts from C57BL/6 mice were transplanted into Bm12 mice (class II mismatch). 4-1BB expression was induced on CD4⁺ and CD8⁺ splenocytes in allografts after cardiac transplantation. 4-1BBL was detected in the vessel wall of the rejecting cardiac allograft and in cultured smooth muscle cells (SMCs) stimulated with fetal calf serum. Recipients were injected intraperitoneally with 4-1BBIg every 7 days for 8 weeks. GAD was significantly attenuated by 4-1BBIg treatment (luminal occlusion, 15.4 ± 3.1% versus control IgG treatment, 75.6 ± 4.6%, <i>P</i>

著者

• Uede Toshimitsu

  Division Of Molecular Immunology Institute For Genetic Medicine Hokkaido University

• Isobe Mitsuaki

  Departement Of Cardiovascular Medicine Tokyo Medical And Dental University

• Maejima Yasuhiro

  Department Of Cardiovascular Medicine Tokyo Medical And Dental University

• Haga Takaaki

  Department of Cardiovascular Medicine, Tokyo Medical and Dental University

• Haraguchi Go

  Department Of Cardiology Tokyo Women's Medical University

• Saiki Hitoshi

  Department of Cardiovascular Medicine, Tokyo Medical and Dental University

• Kosuge Hisanori

  Department Of Cardiovascular Medicine

• Suzuki Jun-ichi

  Department Of Advanced Clinical Science And Therapeutics Graduate School Of Medicine University Of T

• Haga Takaaki

  Department Of Cardiology And Cardiovascular Surgery Shinkyo Hospital

• Ishihara Takashi

  Department Of Applied Physics Nagoya University

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