title: Donor-strain-derived immature dendritic cell pre-treatment induced hyporesponsiveness against allogeneic antigens.
abstract: The maturation of antigen-presenting dendritic cells (DCs) serves as an important determinant for the regulation of immunity, and overall immune response. We hypothesized that a reduced immune response to donor alloantigens and improved allograft survival could be induced by pre-treating recipients with bone-marrow-derived donor-strain fixed immature DCs (FIDCs). Donor-strain-derived mature and immature DCs were fixed before grafting to ensure that they possessed a stable immunogenic phenotype. The fixed mature DCs effectively induced allogeneic T-cell proliferation in recipients, whereas FIDCs were unable to elicit an allogeneic T-cell response. T cells that had previously been exposed to FIDCs maintained naïve phenotypes and were unable to extensively divide after injection into lethally irradiated donor-strain mice. The pre-treatment of recipients with donor-strain FIDCs markedly prolonged the survival of islet as well as skin allografts. However, T-cell hyporesponsiveness induced by FIDC injection was abrogated by the depletion of CD4(+) CD25(+) T cells. Consequently, FIDC-induced T-cell hyporesponsiveness could reflect anergy rather than specific deletion. Our findings suggest that FIDCs of donor strain could be used to induce long-term graft survival.
authors.affiliation: Kidney Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hee Gyung
authors.initials: HG
authors.lastname: Kang
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yang
authors.forename: Se Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Wenda
authors.initials: W
authors.lastname: Gao
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005557:Formaldehyde / Q000737:chemistry; D006085:Graft Survival / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors; D016707:Tissue Fixation; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D006183:H-2 Antigens; D007519:Isoantigens; D005557:Formaldehyde