Physiological and pathological functions of TNF/TNF receptor family molecules.

(1)We已经鉴定了一种名为BSAC的新型转录激活因子，其抑制TNF诱导的细胞死亡。我们还发现TRAF介导的NF-κB活化抑制TNF诱导的ROS积累，这导致JNK活化延长和坏死性细胞死亡。(2)We已经揭示FasL介导由高剂量抗原施用或T.克氏感染我们还揭示了FasL参与结肠炎和肺炎的发病机制。此外，我们还鉴定了猴FasL并建立了检测系统。(3)We已经揭示了TRAIL在针对肿瘤发展和转移的免疫监视以及BMT后GVT效应中的关键作用。我们还证实，阻断NF-κB活化可使各种肿瘤细胞对TRAIL诱导的凋亡敏感。此外，我们已经发现TRAIL可以通过诱导未成熟树突状细胞和浆细胞的凋亡来发挥免疫抑制作用。(4)We已经发现抗死亡诱导的激动性mAb 关于我们 利用小鼠TRAIL受体DR 5的Fc部分募集宿主抗原呈递细胞，不仅可以诱导肿瘤细胞对TRAIL敏感的肿瘤细胞的短暂消退，而且还可以诱导肿瘤特异性CTL，后者还可以清除TRAIL抗性的变异体。(5)We已经揭示了TNF受体家族的新成员Fn 14可以介导TWEAK诱导的细胞死亡。我们还发现了TWEAK/Fn 14对内皮细胞和上皮细胞的促炎功能。此外，我们已经通过使用新产生的单克隆抗体的小鼠TWEAK/Fn 14的表达和功能的特点。(6)We已经发现由肿瘤细胞上的CD 70介导的CD 27介导的NK细胞活化可以以IFN-γ依赖性方式诱导肿瘤特异性T细胞应答。我们还发现，CD 70在活化的树突状细胞诱导的CD 4 T细胞非依赖性CTL和CD 8 T细胞诱导的CD 28非依赖性心脏移植排斥反应中起关键作用。(7)We已经发现OX 40 L在同种异体移植排斥反应和GVHD、结肠炎和哮喘的发病机制中起关键作用。(8)We已经通过使用新产生的mAb表征了小鼠4-1BBL的表达和功能。(9)We揭示了CD 30 L在CD 4 T细胞介导的GVHD发病机制和对鸟分枝杆菌的保护性免疫中的关键作用。（10）我们通过使用新产生的mAb表征了小鼠TRANCE/RANK的表达和功能。我们还发现TRANCE表达质粒作为遗传佐剂的有效活性。少

(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 … More 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