Please use this identifier to cite or link to this item:
Scopus Web of ScienceĀ® Altmetric
Full metadata record
DC FieldValueLanguage
dc.contributor.authorCoates, P.-
dc.contributor.authorKrishnan, R.-
dc.contributor.authorKireta, S.-
dc.contributor.authorJohnston, J.-
dc.contributor.authorRuss, G.-
dc.identifier.citationGene Therapy (Basingstoke), 2001; 8(16):1224-1233-
dc.description.abstractHuman myeloid DC were generated from peripheral blood mononuclear cells by monocyte adhesion and subsequent culture with rhGM-CSF and rhIL-4. We transduced immature (day 5 of culture) myeloid DC with an E1-deleted replication-deficient adenoviral vector encoding the cytokine IL-10 (AdV IL-10) and a control adenovirus MX-17 (AdV MX 17). Human DC transduced with AdV IL-10 showed inhibition of the mixed leukocyte culture, reduced cell surface expression of co-stimulatory molecules (CD80/CD86) and were unable to produce the potent allo-stimulatory cytokine, interleukin-12. In order to test the in vivo properties of these cells a humanized immunodeficient mouse skin transplantation model was developed. Immunodeficient NOD-scid mice were engrafted with human skin, reconstituted via intraperitoneal injection with allogeneic mononuclear cells (MNC) mixed with 1 x 10(6) DC that were autologous to the skin donor and that had been transduced with either AdV IL-10 or AdV MX-17. Skin grafts were removed at day 7 and 14 after reconstitution and studied histologically for evidence of rejection. In animals that received DC modified with AdV IL-10 there was reduced skin graft rejection as characterized by reduced mononuclear cell infiltration and less dermo-epidermal junction destruction compared with those animals that received DC modified with the control virus alone. Injection of equivalent numbers of donor-derived fibroblasts transduced with AdV IL-10 were ineffective at modifying rejection of skin grafts. Immunosuppressive cytokine gene therapy targeting human DC is a novel means of inhibition of the alloimmune response.-
dc.publisherNature Publishing Group-
dc.subjectDendritic Cells-
dc.subjectMice, Inbred NOD-
dc.subjectMice, SCID-
dc.subjectSkin Transplantation-
dc.subjectTransplantation, Heterologous-
dc.subjectCell Separation-
dc.subjectTransduction, Genetic-
dc.subjectModels, Animal-
dc.subjectGraft Rejection-
dc.subjectGenetic Vectors-
dc.subjectGenetic Therapy-
dc.titleHuman myeloid dendritic cells transduced with an adenoviral interleukin-10 gene construct inhibit human skin graft rejection in humanized NOD-scid chimeric mice-
dc.typeJournal article-
Appears in Collections:Aurora harvest 4
Medicine publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.