title: Ex vivo-expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts.
abstract: Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide-major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive thymocytes. For peripheral tolerance, injection of FLDCs induced donor-specific T-cell unresponsiveness and prolonged survival of donor-derived skin grafts. Tolerance induction by adoptive transfer of FLDCs could be a useful approach for promoting graft acceptance after organ transplantation.
authors.affiliation: Division of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science, Tokyo, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Yamano
authors.forename: Sho
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tahara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nitta
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kishimoto
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007267:Injections; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D058985:Side-Population Cells / Q000166:cytology / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D000939:Epitopes; D008565:Membrane Proteins; C084881:flt3 ligand protein