The Inhibitory Effects of Mouse ICOS-Ig Gene-Modified Mouse Dendritic Cells on T Cells

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The main approach to reduce graft rejection has been focused on the development of immunosuppressiveagents at present.Although these strategies have reportedly reduced graft rejection,there has been a reciprocalincrease in more severe immunosuppression and lethal infections,as well as severe side effects.Blockade ofcostimulatory 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 cellscould prolong allograft survival.In this study mouse DCs(mDCs)were transfected with the recombinantplasmid pcDNA3.0 containing mouse inducible costimulator-Ig(mICOS-Ig) cDNA by electroporation.Thetransient expression of mICOS-Ig in mDC could be detected by ELISA and SDS-PAGE.Mouse ICOS-Ig fusionprotein expressed in mDC and mICOS-Ig gene-modified mDC could inhibit lymphocyte proliferation in mixedlymphocyte culture(MLC)in vitro.Furthermore,mICOS-Ig gene-modified mDC could inhibit lymphocyteproliferation in recipient mice.These results suggested that mICOS-Ig gene-modified mDC exerted inhibitoryeffects on T cells,and might be suitable for treatment or prevention of graft rejection and immunopathologicdiseases.Cellular & Molecular Immunology.2004;1(2):153-157. The main approach to reducing graft rejection has been on the development of immunosuppressive agents in present. Although these strategies have reportedly reduced graft rejection, there has been 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. Future, it has been shown that infusion of dendritic cells (DCs) with a potent negative regulatory ability for T cells can prolong allograft survival. In this study mouse DCs (mDCs) were transfected with the recombinant plasmids 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 was expressed in mDC and mICOS-Ig gene-modified mDC could inhibit lymphocyte proliferation in mixed lymphocyte culture (MLC) in vitro.Furthermore, mICOS-Ig gene-modifi ed mDC could inhibit lymphocyteproliferation 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.
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