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dc.contributor.authorIerino, Francesco Len
dc.contributor.authorMulley, Williamen
dc.contributor.authorDodge, Natalieen
dc.contributor.authorLi, Yu Qinen
dc.contributor.authorMouhtouris, Effieen
dc.contributor.authorChristiansen, Daleen
dc.contributor.authorSandrin, Mauro Sen
dc.identifier.citationImmunology and Cell Biology 2010; 88(8): 846-50en
dc.description.abstractDendritic cells (DCs) and CTLA4Ig are important in regulating T-cell responses and therefore represent potential therapeutic tools in transplantation. In this study, CTLA4Ig was expressed in a C57BL/6 murine DC line (JAWS II) by lentiviral transduction and these cells were used to examine T-cell immunomodulatory effects in vitro and in vivo. A lower stimulation index to C57BL/6 was observed with splenocytes from BALB/c mice primed with JAWS II-CTLA4Ig compared with control JAWS II-green fluorescent protein (JAWS II-GFP). Mice primed with JAWS II-CTLA4Ig cells had significantly prolonged antigen-specific C57BL/6 skin graft survival compared with either JAWS II-GFP-primed or naïve mice (median 13, 11 and 11 days, respectively, P=0.0001). Furthermore, JAWS II-CTLA4Ig-primed mice that had been previously transplanted with skin grafts were re-transplanted with skin grafts 6 months later without immune manipulation. These mice demonstrated specific prolongation of second-set rejection responses, indicating systemic immune modulation induced by genetically modified DC. The mechanism was not due to expression of indoleamine 2,3-dioxygenase or induction of circulating regulatory T cells as assessed by flow cytometry of the peripheral blood lymphocytes. This potent effect demonstrated with skin grafts and second-set responses highlights the potential use of this strategy for transplantation more generally.en
dc.subject.otherCell Growth Processes.genetics.immunologyen
dc.subject.otherCell Lineen
dc.subject.otherDendritic Cells.immunology.metabolism.pathologyen
dc.subject.otherGraft Survival.geneticsen
dc.subject.otherImmunologic Memory.geneticsen
dc.subject.otherLymphocyte Activation.geneticsen
dc.subject.otherLymphocyte Culture Test, Mixeden
dc.subject.otherMice, Inbred BALB Cen
dc.subject.otherMice, Inbred C57BLen
dc.subject.otherSkin Transplantationen
dc.titleDendritic cells expressing soluble CTLA4Ig prolong antigen-specific skin graft survival.en
dc.typeJournal Articleen
dc.identifier.journaltitleImmunology and cell biologyen
dc.identifier.affiliationDepartment of Nephrology, Austin Health, Heidelberg, Victoria, Australiaen
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