The main approach to reduce graft rejection has been focused on the development of immunosuppressive agents at present.Although these strategies have reportedly reduced graft rejection,there has been a reciprocal incr...The main approach to reduce graft rejection has been focused on the development of immunosuppressive agents at present.Although these strategies have reportedly reduced graft rejection,there has been a reciprocal increase in more severe immunosuppression and lethal infections,as well as severe side effects.Blockade of costimulatory T cell response has been proved as one of useful strategies to reduce graft rejection.Furthermore, it has been shown that infusion of dendritic cells(DCs)with a potent negative regulatory ability for T cells could prolong allograft survival.In this study mouse DCs(mDCs)were transfected with the recombinant plasmid pcDNA3.0 containing mouse inducible costimulator-Ig(mICOS-Ig) cDNA by electroporation.The transient expression of mICOS-Ig in mDC could be detected by ELISA and SDS-PAGE.Mouse ICOS-Ig fusion protein expressed in mDC and mICOS-Ig gene-modified mDC could inhibit lymphocyte proliferation in mixed lymphocyte culture(MLC)in vitro.Furthermore,mICOS-Ig gene-modified mDC could inhibit lymphocyte proliferation in recipient mice.These results suggested that mICOS-Ig gene-modified mDC exerted inhibitory effects on T cells,and might be suitable for treatment or prevention of graft rejection and immunopathologic diseases.Cellular & Molecular Immunology.2004;1(2):153-157.展开更多
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 β cell death.Fas-associated death domain prot...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 β 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 β 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.Cellular & Molecular Immunology.2004;1(5):383-386.展开更多
基金surpported by National Key Basic Research Program of China(No.CB510008)
文摘The main approach to reduce graft rejection has been focused on the development of immunosuppressive agents at present.Although these strategies have reportedly reduced graft rejection,there has been a reciprocal increase in more severe immunosuppression and lethal infections,as well as severe side effects.Blockade of costimulatory T cell response has been proved as one of useful strategies to reduce graft rejection.Furthermore, it has been shown that infusion of dendritic cells(DCs)with a potent negative regulatory ability for T cells could prolong allograft survival.In this study mouse DCs(mDCs)were transfected with the recombinant plasmid pcDNA3.0 containing mouse inducible costimulator-Ig(mICOS-Ig) cDNA by electroporation.The transient expression of mICOS-Ig in mDC could be detected by ELISA and SDS-PAGE.Mouse ICOS-Ig fusion protein expressed in mDC and mICOS-Ig gene-modified mDC could inhibit lymphocyte proliferation in mixed lymphocyte culture(MLC)in vitro.Furthermore,mICOS-Ig gene-modified mDC could inhibit lymphocyte proliferation in recipient mice.These results suggested that mICOS-Ig gene-modified mDC exerted inhibitory effects on T cells,and might be suitable for treatment or prevention of graft rejection and immunopathologic diseases.Cellular & Molecular Immunology.2004;1(2):153-157.
基金This study was supported by National Key Basic Research Program of China(No.CB5 10008)National Natural Science foundation(No.30300166).
文摘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 β 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 β 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.Cellular & Molecular Immunology.2004;1(5):383-386.
