title: DX5(+)CD4(+) T cells modulate cytokine production by CD4(+) T cells towards IL-10 via the production of IL-4.
abstract: CD4(+) Th cells play a critical role in orchestrating the adaptive immune response. Uncontrolled Th1 responses are implicated in the pathogenesis of autoimmune diseases. T cells with immune-modulatory properties are beneficial for inhibiting such inflammatory responses. Previously we demonstrated that repetitive injections of immature DC induce expansion of DX5(+)CD4(+) T cells, which upon adoptive transfer show potent regulatory properties in murine collagen-induced arthritis as well as in delayed-hypersensitivity models. However, their regulatory mechanism remains to be defined. Here, we analyzed the effect of DX5(+)CD4(+) T cells on other CD4(+) T cells in vitro. Although proliferation of naïve CD4(+) T cells upon antigenic triggering was not altered in the presence of DX5(+)CD4(+) T cells, there was a striking difference in cytokine production. In the presence of DX5(+)CD4(+) T cells, an IL-10-producing CD4(+) T-cell response was induced instead of a predominant IFN-γ-producing Th1 response. This modulation did not require cell-cell contact. Instead, IL-4 produced by DX5(+)CD4(+) T cells was primarily involved in the inhibition of IFN-γ and promotion of IL-10 production by CD4(+) T cells. Together, our data indicate that DX5(+)CD4(+) T cells modulate the outcome of Th-responses by diverting Th1-induction into Th responses characterized by the production of IL-10.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wanda G H
authors.initials: WG
authors.lastname: Han
authors.forename: Ellen I H
authors.initials: EI
authors.lastname: van der Voort
authors.forename: Hanane
authors.initials: H
authors.lastname: el Bannoudi
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: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma