title: Alloantigen-specific T-cell hyporesponsiveness induced by dnIKK2 gene-transfected recipient immature dendritic cells.
abstract: Immature dendritic cells (iDCs) have been shown to be able to induce peripheral T-cell tolerance through distinct pathways. Here, we investigated the tolerogenic property of recipient iDCs whose maturation was arrested by a dominant negative mutant of inhibitor of nuclear factor kappa-B kinase 2 (dnIKK2) gene. We found that dnIKK2-iDCs presented a typical semi-mature morphology and expressed lower levels of CD80 and CD86, slightly higher MHC-II than untransfected iDCs. The expression of these molecules had no significant change even dnIKK2-iDCs were pulsed by donor antigen. In primary mixed leukocyte reaction (MLR), dnIKK2-iDCs exhibited impaired ability to stimulate allogeneic T-cells, but induced CD4(+)CD25(-) T-cell formation. In co-culture MLR, these CD4(+)CD25(-) T-cells suppressed T-cell alloreaction in an antigen-specific manner. Besides, CD4(+)CD25(-) T-cells inhibited IL-2 and IFN-γ release, whereas promoted IL-10 and TGF-β secretion. These data suggested recipient dnIKK2-iDCs could maintain peripheral tolerance through down-regulating costimulatory molecule expressions and inducing CD4(+)CD25(-) T-cell formation.
authors.affiliation: Department of Urology, Shaoxing Central Hospital, Shaoxing, Zhejiang 312030, PR China; Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China.
authors.forename: Cai-bin
authors.initials: CB
authors.lastname: Fan
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China; Department of Urology, Suzhou Kowloon Hospital of Shanghai Jiaotong University School of Medicine, Suzhou, Jiangsu 215021, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Shaoxing Central Hospital, Shaoxing, Zhejiang 312030, PR China.
authors.forename: Qing-ping
authors.initials: QP
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China.
authors.forename: Ke-lin
authors.initials: KL
authors.lastname: Du
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China.
authors.forename: Duan-gai
authors.initials: DG
authors.lastname: Wen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China. Electronic address: ouyangjun99@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051550:I-kappa B Kinase / Q000235:genetics* / Q000276:immunology; D007108:Immune Tolerance; D007519:Isoantigens; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009154:Mutation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014162:Transfection
chemical_list: D016207:Cytokines; D007519:Isoantigens; D051550:I-kappa B Kinase; C518254:Ikbkb protein, rat
keywords: Immature dendritic cells; Immune tolerance; Transplantation; dnIKK2