Article: article from journal or magazin.
Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells.
Journal of Experimental Medicine
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Human thymic stromal lymphopoietin (TSLP) is a novel epithelial cell-derived cytokine, which induces dendritic cell (DC)-mediated CD4+ T cell responses with a proallergic phenotype. Although the participation of CD8+ T cells in allergic inflammation is well documented, their functional properties as well as the pathways leading to their generation remain poorly understood. Here, we show that TSLP-activated CD11c+ DCs potently activate and expand naive CD8+ T cells, and induce their differentiation into interleukin (IL)-5 and IL-13-producing effectors exhibiting poor cytolytic activity. Additional CD40L triggering of TSLP-activated DCs induced CD8+ T cells with potent cytolytic activity, producing large amounts of interferon (IFN)-gamma, while retaining their capacity to produce IL-5 and IL-13. These data further support the role of TSLP as initial trigger of allergic T cell responses and suggest that CD40L-expressing cells may act in combination with TSLP to amplify and sustain pro-allergic responses and cause tissue damage by promoting the generation of IFN-gamma-producing cytotoxic effectors.
Antigens, CD11c/immunology, Antigens, CD11c/metabolism, CD40 Ligand/metabolism, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cell Differentiation/physiology, Cells, Cultured, Cytokines/metabolism, Dendritic Cells/cytology, Dendritic Cells/immunology, Humans, Hypersensitivity/immunology, Inflammation/immunology, Interferon-gamma/metabolism, Interleukin-13/metabolism, Interleukin-5/metabolism, Lymphocyte Activation
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