title: Prolongation of rat renal allograft survival by CD4⁺CD25⁻ T cells induced by recipient dendritic cells transfected with IKK2dn.
abstract: Previous studies have demonstrated that recipient-derived immature dendritic cells transfected by recombinant adenovirus-mediated IKK2dn (Adv‑IKK2dn) and loaded with donor splenocyte lysate generate CD4+CD25- T cells (Adv-IKK2dn-CD4+CD25- T cells). These cells may inhibit T cell responses in vitro. In the present study, Lewis (LW) rats were administered with an intravenous injection of naive CD4+ T cells, empty adenovirus (Adv-0)-dendritic cell-generated CD4+CD25- T cells (Adv-0-CD4+CD25- T cells), Adv-IKK2dn-CD4+CD25- T cells or an equal volume of normal saline, seven days prior to transplantation. The potency and the mechanism of action of Adv-IKK2dn-CD4+CD25- T cells was analyzed, as well as an investigation of their tolerogenic properties in vivo. Administration of Adv-IKK2dn-CD4+CD25- T cells in vivo to LW rats was observed to markedly prolong the survival of a kidney allograft from Brown Norway rats. Furthermore, the Adv-IKK2dn-CD4+CD25- T cell-treated group exhibited significantly reduced levels of interleukin (Il)-2 and interferon-γ production and increased Il-10 and transforming growth factor-β (TGF-β) secretion. The serum creatinine levels remained at low levels in the Adv-IKK2dn-CD4+CD25- T cell-treated group. Their ability to induce allogeneic T cell proliferation was markedly reduced compared with the other groups. These observations indicated that Adv-IKK2dn-CD4+CD25- T cells induce prolongation of kidney allograft survival in vivo, which is hypothesized to be due to the high expression levels of Il-10 and TGF-β.
authors.affiliation: Department of Urology, The Fourth People's Hospital of Changzhou, Changzhou, Jiangsu 213032, P.R. China.
authors.forename: Shen
authors.initials: S
authors.lastname: Wang
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Chen
authors.forename: Cai-Bin
authors.initials: CB
authors.lastname: Fan
authors.forename: Duan-Gai
authors.initials: DG
authors.lastname: Wen
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D064591:Allografts; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005799:Genes, Dominant / Q000235:genetics; D005822:Genetic Vectors / Q000008:administration & dosage; D006085:Graft Survival / Q000276:immunology*; D051550:I-kappa B Kinase / Q000235:genetics*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D051550:I-kappa B Kinase; C518254:Ikbkb protein, rat