title: Donor antigen-loaded IKK2dn gene-modified dendritic cells prolong allograft survival.
abstract: Dendritic cells (DC) are key factors in regulating immune responses, and they induce immune response or tolerance depends on its maturation states. Previous studies demonstrated that blocking IKK2 in bone marrow-derived dendritic cells (BMDC) by adenoviral transfection with a kinase-defective dominant negative form of IKK2 (IKK2dn) could inhibit NF-kappaB activation and impair DC maturation. Here, we transfected IKK2dn into recipient rat (Lewis) BMDC by adenovirus vector (Adv-IKK2dn-DC) and found that Adv-IKK2dn-DC had reduced B7-2 and B7-1 expression under alloantigen stimulation. Their ability to induce allogeneic T-cell proliferation was markedly reduced in comparison with uninfected DC. A higher IL-10 secretion and a lower IFN-gamma secretion were detected in Adv-IKK2dn-DC-stimulated allogenic T cells. Furthermore, we showed that Adv-IKK2dn-DC pulsed with BN (Brown Norway rats) splenocyte lysates markedly prolonged the survival of renal allografts in an antigen-specific manner. These findings suggested that Adv-IKK2dn-DC loaded with BN antigen could suppress anti-alloimmune response and induce tolerance to allografts, which provided an experimental base for immune tolerance induction by recipient DC loaded with donor antigens. Our finding may provide a more feasible strategy for deceased-donor renal transplantation.
authors.affiliation: Department of Urology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Ouyang
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.forename: D
authors.initials: D
authors.lastname: Wen
authors.forename: J
authors.initials: J
authors.lastname: Hou
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Shi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors; D006085:Graft Survival / Q000276:immunology*; D051550:I-kappa B Kinase / Q000235:genetics*; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D051550:I-kappa B Kinase; D007371:Interferon-gamma; D016753:Interleukin-10; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C518254:Ikbkb protein, rat