| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
(1)We have identified a novel transcriptional activator named BSAC, which suppresses TNF-induced cell death. We have also revealed that TRAF-mediated NF-κB activation suppresses TNF-induced ROS accumulation, which leads to prolonged JNK activation and necrotic cell death.
(2)We have revealed that FasL mediates immunosuppression induced by high-dose antigen administration or T. cruzi infection. We have also revealed the involvement of FasL in pathogenesis of colitis and pneumonia. Moreover, we have identified monkey FasL and established its detection system.
(3)We have revealed critical role for TRAIL in immune surveillance against tumor development and metastasis, and GVT effect after BMT. We have also demonstrated that blockade of NF-κB activation can sensitize various tumor cells to TRAIL-induced apoptosis. Moreover, we have found that TRAIL can act immunosuppressive by inducing apoptosis in immature dendritic cells and plasma cells.
(4)We have found that agonistic mAb against death-ind
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ucing mouse TRAIL receptor (DR5) can not only induce regression of TRAIL-sensitive tumors transiently but also induce tumor-specific CTL, which can also eradicate TRAIL-resistant variants, via recruitment of host antigen-presenting cells by its Fc portion.
(5)We have revealed that a new member of TNF receptor family, Fn14, can mediate TWEAK-induced cell death. We have also found pro-inflammatory function of TWEAK/Fn14 against endothelial and epithelial cells. Moreover, we have characterized the expression and function of mouse TWEAK/Fn14 by using newly generated mAbs.
(6)We have found that CD27-mediated NK cell activation by CD70 on tumor cells can induce tumor-specific T cell responses in IFN-γ-dependent manner. We have also revealed that CD70 plays critical role in CD4 T cell-independent CTL induction by activated dendrific cells and in CD28-independent cardiac allograft rejection by CD8 T cells.
(7)We have found that OX40L plays critical role in allograft rejection and pathogenesis of GVHD, colotis, and asthma.
(8)We have characterized the expression and function of mouse 4-1BBL by using newly generated mAbs.
(9)We have revealed critical role of CD30L in pathogenesis of CD4 T cell-mediated GVHD and protective immunity to M.avium.
(10)We have characterized the expression and function of mouse TRANCE/RANK by using newly generated mAbs. We have also found potent activity of TRANCE-expressing plasmid as a genetic adjuvant. Less
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