IL-1 Receptor Signaling Is Required at Multiple Stages of Sensitization and Elicitation of the Contact Hypersensitivity Response

Autor: Anton V. Gorbachev, Robert L. Fairchild, Danielle D. Kish
Rok vydání: 2012
Předmět:
Zdroj: The Journal of Immunology. 188:1761-1771
ISSN: 1550-6606
0022-1767
Popis: Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten skin sensitization and challenge. The points at which IL-1R signaling is required during this complex, multistep immune response have not been clearly delineated. The role of IL-1R signaling during 2, 4 dinitro-1-fluorobenezene (DNFB) sensitization to induce hapten-specific CD8 effector T cells and in the trafficking of the effector T cells to the DNFB challenge site to elicit the response were investigated using IL-1R deficient mice. DNFB-sensitized IL-1R−/− mice had low CHS responses to hapten challenge that were caused in part by marked decreases in hapten-specific CD8 T cell development to IL-17– and IFN-γ–producing cells during sensitization. Hapten-primed wild type CD8 T cell transfer to naive IL-1R−/− mice did not result in T cell activation in response to hapten challenge, indicating a need for IL-1R signaling for the localization or activation, or both, of the CD8 T cells at the challenge site. Decreased CD8 T cell priming in sensitized IL-1R−/− mice was associated with marked decreases in hapten-presenting dendritic cell migration from the sensitized skin to draining lymph nodes. Transfer of hapten-presenting dendritic cells from wild type donors to naive IL-1R−/− mice resulted in decreased numbers of the dendritic cells in the draining lymph nodes and decreased priming of hapten-specific CD8 T cells compared with dendritic cell transfer to naive wild type recipients. These results indicate that IL-1R signaling is required at multiple steps during the course of sensitization and challenge to elicit CHS.
Databáze: OpenAIRE