Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection.

摘要: Manipulation of human T cell functioning by delivery macromolecules such as DNA, RNA, or protein is limited, unless the cells have been stimulated electropermeabilized. To achieve successful adaptation and survival a grafted organ, alloreactive that induce graft rejection must be regulated. Corticosteroids, calcineurin inhibitors, mTOR which are systemic immunosuppressants, currently used for transplantation, with significant side effects. In this study, we demonstrated cell-permeable peptide (CPP), dNP2, could efficiently deliver proteins into CD4 CD8 cells. We confirmed regulatory cytoplasmic domain CTLA-4 conjugated dNP2 (dNP2-ctCTLA-4) in activation, proliferation, chemokine receptor expression. utilized skin allograft system SCID/beige mice to examine whether dNP2-ctCTLA-4 inhibit controlling responses. The tissue inflammation, allogeneic infiltration, blood cytokine level was markedly reduced dNP2-ctCTLA-4, resulting transplantation. addition, it also inhibited alloresponses against microvessels formed form Bcl-2-transduced umbilical vein endothelial implanted Balb/c Rag1-/-/IL-2Rγ-/- double knockout (DKO) mice, assessed infiltration granzyme B These results collectively suggest conjugation offers valuable tool delivering like cells, novel agent shows potential responses allow tissues.