FADDdel-GFP modified mouse insulinoma cells counteract the cytotoxicity of reactive T cells.
IDDM results from pancreatic beta cell destruction by islet-reactive T cells, a process that involves beta cell apoptosis. Fas-FasL pathway plays a major role in pancreatic beta cell death. Fas-associated death domain protein (FADD), the component of the tumor necrosis factor receptor type 1 (TNFR1) and Fas signaling complexes, is involved in TNFR1- and Fas-induced apoptosis. Inhibiting the function of FADD will lead to blocking downstream apoptosis signal, which protects pancreatic beta cells from destruction by Fas-FasL pathway. In this study we constructed eukaryotic expressing vector of fusional protein FADDdel-GFP named pFADDdel-GFP. After pFADDdel-GFP was transfected into NIT, the expression of FADDdel-GFP in NIT was detected by fluorescence microscopy and the resistance of NIT transfected with pFADDdel-GFP to cytotoxicity mediated by special T cells was detected by FACS and MTT. The results showed that NIT modified by pFADDdel-GFP obviously resisted cytotoxicity mediated by special T cells. Therefore, it may be useful in the prevention or treatment of IDDM by intervening Fas-FasL pathway.
Hu
Ping
P
Department of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Guohua
G
Zhu
Xiaohua
X
Yang
Jing
J
Zhu
Huifen
H
Xu
Zihui
Z
Liao
Wenjun
W
Liu
Xiao
X
Xu
Fen
F
Yin
Jiao
J
Shen
Guan Xin
GX
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology; D007340:Insulinoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D053319:Tumor Necrosis Factor Decoy Receptors; D048069:Tumor Necrosis Factors / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C505534:Fadd protein, mouse; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D048069:Tumor Necrosis Factors; D019014:fas Receptor; C069521:recombinant human tumor necrosis factor-binding protein-1