title: Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells.
abstract: The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83(-) and mature CD83(+) human DCs were used for stimulation of naive, allogeneic CD4(+) T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte-associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon gamma, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10-producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10-producing T cell regulatory 1-like cells by immature DCs.
authors.affiliation: Department of Dermatology, University of Mainz, D-55101 Mainz, Germany. jonuleit@hautklinik.klinik.uni-mainz.de
authors.forename: H
authors.initials: H
authors.lastname: Jonuleit
authors.forename: E
authors.initials: E
authors.lastname: Schmitt
authors.forename: G
authors.initials: G
authors.lastname: Schuler
authors.forename: J
authors.initials: J
authors.lastname: Knop
authors.forename: A H
authors.initials: AH
authors.lastname: Enk
mesh_terms: D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D000941:Antigens; D015703:Antigens, CD; D007136:Immunoglobulins; D016753:Interleukin-10; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen