IL1 is Required for CD8 T Cell Stimulation of Endothelial Cells to Produce KC in Contact Hypersensitivity (89.13)

Abstract

Abstract Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten sensitization and challenge of the skin. Elicitation of CHS is initiated when hapten-primed CD8 T cells producing IFN-γ and IL-17 traffic to the challenge site and stimulate endothelial cells (EC) to produce CXCL1/KC. KC is required for the neutrophil recruitment directing CD8 T cell infiltration through the EC where they are activated to induce the edema of CHS. This study investigated the role of IL1 in the CD8 T cell priming and elicitation of CHS. Both KC production and neutrophil infiltration into the skin challenge site as well as CHS responses were low-absent following challenge of sensitized IL1R-/- vs. wild-type (WT) mice. Sensitization of IL1R-/- mice induced marked decreases in migration of hapten-presenting Langerhans cells into the skin-draining lymph nodes and priming of CD8+ T cells producing IFN-γ or IL-17 vs. WT mice. Transfer of WT hapten-presenting Langerhans cells to IL1R-/- mice did not correct these defects. Transfer of primed WT CD8 T cells to naïve IL1R-/- mice also failed to induce KC production to hapten challenge. These results indicate that IL1 signaling is required for optimal migration of hapten-presenting dendritic cells from the sensitized skin to the draining lymph nodes, for hapten-primed CD8 T cell priming, and for activation of these CD8 T cells by hapten-presenting endothelial cells in the challenge site to induce CXCL1/KC production and the CHS response.