Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells.
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.[1]References
- Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells. Gilliet, M., Soumelis, V., Watanabe, N., Hanabuchi, S., Antonenko, S., de Waal-Malefyt, R., Liu, Y.J. J. Exp. Med. (2003) [Pubmed]
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