title: DX5+ CD4+ T cells modulate CD4+ T-cell response via inhibition of IL-12 production by DCs.
abstract: DX5(+) CD4(+)  T cells have been shown to dampen collagen-induced arthritis and delayed-type hypersensitivity reactions in mice. These cells are also potent modulators of T-helper cell responses through direct effects on CD4(+)  T cells in an IL-4 dependent manner. To further characterize this T-cell population, we studied their effect on DCs and the potential consequences on T-cell activation. Here, we show that mouse DX5(+) CD4(+)  T cells modulate DCs by robustly inhibiting IL-12 production. This modulation is IL-10 dependent and does not require cell contact. Furthermore, DX5(+) CD4(+)  T cells modulate the surface phenotype of LPS-matured DCs. DCs modulated by DX5(+) CD4(+)  T-cell supernatant express high levels of the co-inhibitor molecules PDL-1 and PDL-2. OVA-specific CD4(+)  T cells primed with DCs exposed to DX5(+) CD4(+)  T-cell supernatant produce less IFN-γ than CD4(+)  T cells primed by DCs exposed to either medium or DX5(-) CD4(+)  T-cell supernatant. The addition of IL-12 to the co-culture with DX5(+)  DCs restores IFN-γ production. When IL-10 present in the DX5(+) CD4(+)  T-cell supernatant is blocked, DCs re-establish their ability to produce IL-12 and to efficiently prime CD4(+)  T cells. These data show that DX5(+) CD4(+)  T cells can indirectly affect the outcome of the T-cell response by inducing DCs that have poor Th1 stimulatory function.
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Hanane
authors.initials: H
authors.lastname: el Bannoudi
authors.forename: Wanda G H
authors.initials: WG
authors.lastname: Han
authors.forename: Jeroen N
authors.initials: JN
authors.lastname: Stoop
authors.forename: Pascale
authors.initials: P
authors.lastname: Louis-Plence
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma