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• W2069346187 abstract "Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and altered differentiation of keratinocytes in reply to cytokines such as interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha, provided by infiltrating CD4+ and CD8+ T cells and natural killer cells. Infliximab is a chimeric monoclonal antibody that neutralizes both soluble and membrane-bound TNF-alpha, and that may give a long-term disease remission.To determine the in vitro effects of infliximab on CD4+ and CD8+ T cells derived from lesional skin, and on dendritic cells (DCs).Psoriatic T-cell lines were isolated from lesional skin of four patients with psoriasis and assayed for their proliferation, cytokine release and susceptibility to apoptotic stimuli in the presence of graded (1-100 microg mL(-1)) concentrations of infliximab. DCs were differentiated in the presence of infliximab from peripheral blood monocytes. Phenotype was assessed by fluorescence-activated cell sorting and antigen-presenting capacity in functional assays.In vitro activation of psoriatic as well as antigen (nickel)-specific skin-homing T cells was strongly and dose-dependently impaired by infliximab, in terms both of proliferation and of IFN-gamma release. Despite the significant reduction of IFN-gamma secretion, infliximab only marginally affected the release of interleukin (IL)-10 by skin T cells, thus determining a reduction of the IFN-gamma/IL-10 ratio at the site of inflammation. The effects were maximal when T-cell activation occurred in the absence of costimulation, or when T cells were activated by immature compared with mature DCs. In addition, skin-homing CD8+ T cells were more prominently affected by infliximab compared with CD4+ T lymphocytes, both in terms of inhibition of activation and in their susceptibility to apoptosis. Finally, infliximab directly affected the differentiation of monocyte-derived DCs, by inhibiting the expression of CD1a and CD86, and strongly impaired the antigen-presenting capacity of immature and, to a lesser extent, mature DCs.Infliximab directly affects psoriatic T cells and impairs the antigen-presenting capacity of DCs. These effects may help to explain the long-term disease remission obtained with the drug." @default.
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• W2069346187 date "2007-08-01" @default.
• W2069346187 modified "2023-10-06" @default.
• W2069346187 title "Antitumour necrosis factor-? chimeric antibody (infliximab) inhibits activation of skin-homing CD4+ and CD8+ T lymphocytes and impairs dendritic cell function" @default.
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• W2069346187 doi "https://doi.org/10.1111/j.1365-2133.2007.07945.x" @default.
• W2069346187 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17489975" @default.
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