PMID- 21220748 OWN - NLM STAT- MEDLINE DCOM- 20110509 LR - 20220310 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 117 IP - 9 DP - 2011 Mar 3 TI - Ex vivo-expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts. PG - 2640-8 LID - 10.1182/blood-2010-07-293860 [doi] AB - 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. CI - (c) 2011 by The American Society of Hematology FAU - Yamano, Tomoyoshi AU - Yamano T AD - Division of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science, Tokyo, Japan. FAU - Watanabe, Sho AU - Watanabe S FAU - Hasegawa, Hiroyuki AU - Hasegawa H FAU - Suzuki, Toshihiro AU - Suzuki T FAU - Abe, Ryo AU - Abe R FAU - Tahara, Hideaki AU - Tahara H FAU - Nitta, Takeshi AU - Nitta T FAU - Ishimaru, Naozumi AU - Ishimaru N FAU - Sprent, Jonathan AU - Sprent J FAU - Kishimoto, Hidehiro AU - Kishimoto H LA - eng PT - Journal Article DEP - 20110110 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Epitopes) RN - 0 (Membrane Proteins) RN - 0 (flt3 ligand protein) SB - IM MH - Adoptive Transfer MH - Animals MH - Cell Movement MH - Cell Proliferation MH - Clone Cells MH - Dendritic Cells/*cytology/*immunology MH - Epitopes/immunology MH - Graft Survival/*immunology MH - Immune Tolerance/*immunology MH - Injections MH - Membrane Proteins/metabolism MH - Mice MH - Side-Population Cells/cytology/immunology MH - Skin Transplantation/*immunology MH - T-Lymphocytes/cytology/immunology MH - Thymus Gland/cytology MH - Time Factors MH - Transplantation, Homologous EDAT- 2011/01/12 06:00 MHDA- 2011/05/10 06:00 CRDT- 2011/01/12 06:00 PHST- 2011/01/12 06:00 [entrez] PHST- 2011/01/12 06:00 [pubmed] PHST- 2011/05/10 06:00 [medline] AID - S0006-4971(20)39060-1 [pii] AID - 10.1182/blood-2010-07-293860 [doi] PST - ppublish SO - Blood. 2011 Mar 3;117(9):2640-8. doi: 10.1182/blood-2010-07-293860. Epub 2011 Jan 10.