許秉寧臺灣大學：免疫學研究所周詩茵Chou, Shih-YinShih-YinChou2007-11-292018-07-092007-11-292018-07-092004http://ntur.lib.ntu.edu.tw//handle/246246/63343第三號誘餌受體 (DcR3) 是一個新定義的分子，屬於腫瘤壞死因子受體家族中的一員,它是FasL，LIGHT和TL1A的受體。然而對於可溶性DcR3的生物角色並不清楚，最近有一些文獻發現在紅斑性狼瘡 (SLE) 病人可以看到DcR3 mRNA的過度表現。在我們的研究中證明相較於正常人，在SLE病人的血清中的確有看到明顯增高的DcR3蛋白質，暗示著DcR3可能在SLE病人的生理及病理機轉扮演著某種角色。為了探討DcR3在SLE中可能影響的病理機轉，我們想要研究DcR3是否可能直接引起T細胞的活化，並且是否可能抑制活化T細胞所引起的細胞自發性死亡。在我們的結果證明可溶性DcR3與低濃度下的plate-bound anti-CD3抗體共同刺激下，可以增強人類T細胞的增殖，並且促進IL-2和IFN-Decoy receptor 3 (DcR3), a newly member of tumor necrosis factor receptor (TNFR) superfamily, is a receptor for Fas ligand (FasL), LIGHT and TL1A. The biological role of soluble DcR3 is not clear, while DcR3 mRNA has been reported over-expressed in patients with systemic lupus erythematosus (SLE). Here we demonstrated marked elevated serum DcR3 in patients with SLE compared with normal health controls, suggested that DcR3 may play a role in SLE. In order to clarify the possible mechanisms in the pathogenesis of SLE by DcR3, we study whether DcR3 could directly induce T cell activation and whether it could promote survival of activated T cells via inhibiting the activation induced cell death (AICD). Our results demonstrated that soluble DcR3-Fc enhanced human T cell proliferation and increased production of IL-2 and IFN-Table of content Abstract i Abstract (Chinese) ii Chapter I. Introduction Part 1 Decoy receptor 3 (DcR3) 1 Part 2 Costimulation 3 Part 3 Activation-induced cell death (AICD) in T cells 4 Part 4 Systemic Lupus Erythematosus (SLE) 4 Part 5 Aims of the study 6 Chapter II. Materials and methods Part 1. Experimental Procedures 1.1 Antibodies 7 1.2 Reagents 8 1.3 Buffers and solutions 10 1.4 Instruments 12 1.5 cell lines 13 1.6 ELISA Kits 13 1.7 Patients 13 1.8 Others 14 Part 2. Experimental Methods 15 Chapter III. Results Part 1. Serum DcR3 levels in SLE patients were significantly higher than in normal donors 20 Part 2. Generation of soluble recombinant DcR3-Fc fusion protein 20 Part 3. Enhanced human T cell proliferation by soluble DcR3-Fc in conjunction with immobilized suboptimal concentration of anti-CD3 21 Part 4. Increased production of IL-2, IFN-540120 bytesapplication/pdfen-UST 細胞細胞凋亡第三誘餌受體紅斑性狼瘡DcR3SLET cellapoptosis[SDGs]SDG3otherhttp://ntur.lib.ntu.edu.tw/bitstream/246246/63343/1/ntu-93-R91449010-1.pdf