title: Tacrolimus (FK506) treatment of CD34+ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4+ T cells toward Th2 responses.
abstract: The macrolide lactone, tacrolimus (FK506), is utilized in bone marrow transplantation (BMT) to prevent graft-versus-host disease (GVHD). In the current study, we evaluated the ability of FK506 to modify the function of dendritic cells (DCs) derived from CD34+ hematopoietic progenitor cells (HPCs). Comparable to DCs obtained in the absence of FK506, DCs cultured in the presence of FK506 (FK-DCs) had higher expression of CD1a+ and formed a greater number of DC colonies. Despite the same expression of costimulatory molecules, FK-DCs displayed a reduced capacity to stimulate an allogeneic T cell response, and showed significantly lower interleukin (IL)-12 production. While normal DCs pulsed with the exogenous antigen, keyhole limpet hemocyanin (KLH) induced specific Th1-like interferon-gamma(IFN-gamma) producing CD4+ T cell line, FK-DCs induced Th2-like interleukin-4 (IL-4) producing CD4+ T cell line. These data demonstrate the ability of FK506 to induce Th2-promoting function in developing DCs.
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: S
authors.initials: S
authors.lastname: Fujii
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: K
authors.initials: K
authors.lastname: Kawa
authors.forename: A
authors.initials: A
authors.lastname: Yamada
authors.forename: F
authors.initials: F
authors.lastname: Kawano
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D010587:Phagocytosis; D016559:Tacrolimus / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D016559:Tacrolimus