title: Cross-tolerance of recipient-derived transforming growth factor-beta dendritic cells.
abstract: Administration of donor-derived immature dendritic cells (DC) treated with transforming growth factor-beta (TGF-beta) to prevent allograft rejection is not applicable for clinical use. We therefore attempted to explore the use of recipient-derived DC pulsed with donor antigens via the indirect pathway (cross-priming). DC were propagated from C3H (H2(k)) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). TGF-beta (0.2 ng/mL) was added at the initiation of culture. The resultant TGF-beta DC were pulsed with B10 (H2(b)) splenocyte lysate. Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-beta. C3H DC pulsed with B10 antigens stimulated a proliferative response in C3H T cells which was inhibited when DC were treated with TGF-beta, and the cytotoxic T-lymphocyte (CTL) activity was also inhibited. This observation correlated with reduced interferon-gamma (IFN-gamma) and increased IL-10 production. A single injection of TGF-beta DC prolonged allograft survival (median survival time [MST] 18 days vs 10 days in no-DC treatment control; P < .05). These data indicated that an approach utilizing recipient DC as a "vaccine" strategy is possible.
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: M-M
authors.initials: MM
authors.lastname: Tiao
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: L-T
authors.initials: LT
authors.lastname: Huang
authors.forename: C-D
authors.initials: CD
authors.lastname: Liang
authors.forename: C-L
authors.initials: CL
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Tao
authors.forename: J J
authors.initials: JJ
authors.lastname: Fung
authors.forename: S
authors.initials: S
authors.lastname: Qian
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology* / Q000637:transplantation*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis*; D023001:Transplantation Tolerance
chemical_list: D015703:Antigens, CD; D016212:Transforming Growth Factor beta