title: Dendritic cell-derived TNF-alpha is responsible for development of IL-10-producing CD4+ T cells.
abstract: Immature dendritic cells (DCs) appear to be involved in peripheral immune tolerance via induction of IL-10-producing CD4(+) T cells. We examined the role of TNF-alpha in generation of the IL-10-producing CD4(+) T cells by immature DCs. Immature bone marrow-derived DCs from wild type (WT) or TNF-alpha(-/-) mice were cocultured with CD4(+) T cells from OVA specific TCR transgenic mice (OT-II) in the presence of OVA(323-339) peptide. The WT DCs efficiently induced the antigen-specific IL-10-producing CD4(+) T cells, while the ability of the TNF-alpha(-/-) DCs to induce these CD4(+) T cells was considerably depressed. Addition of exogenous TNF-alpha recovered the impaired ability of the TNF-alpha(-/-) DCs to induce IL-10-producing T cells. However, no difference in this ability was observed between TNF-alpha(-/-) and WT DCs after their maturation by LPS. Thus, TNF-alpha appears to be critical for the generation of IL-10-producing CD4(+) T cells during the antigen presentation by immature DCs.
authors.affiliation: Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hirata
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Satoh
authors.forename: Hisako
authors.initials: H
authors.lastname: Ogura
authors.forename: Takashi
authors.initials: T
authors.lastname: Ebihara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Machiko
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.forename: Kazunori
authors.initials: K
authors.lastname: Onoé
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
mesh_terms: D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000276:immunology*
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010047:Ovalbumin