IL-1β, but not IL-1α, is required for antigen-specific T cell activation and the induction of local inflammation in the delayed-type hypersensitivity responses

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Abstract

As IL-1 expression is augmented in delayed-type hypersensitivity (DTH) responses, we analyzed the role of IL-1 in this response. DTH responses against methyl BSA (mBSA) were significantly suppressed in IL-1β-deficient (IL-1β−/−) and IL-1α/β−/− mice, but not in IL-1α−/− mice. In contrast, responses in IL-1R antagonist−/− (IL-1Ra−/−) mice were exacerbated. Lymph node cells derived from mBSA-sensitized IL-1β−/−, IL-1α/β−/− and IL-1R type I (IL-1RI)−/− mice, but not from IL-1α−/− mice, exhibited reduced proliferative responses against mBSA, while these from IL-1Ra−/− mice demonstrated augmented responses. DTH responses in wild-type mice following adoptive transfer of CD4+ T cells from mBSA-sensitized IL-1α/β−/− mice were also reduced, while those in mice given cells derived from IL-Ra−/− mice were increased. DTH responses in IL-1RI−/−, but not IL-1α/β−/−, mice were reduced upon transplantation of mBSA-sensitized CD4+ T cells from wild-type mice. The recall response of mBSA-sensitized CD4+ T cells against mBSA decreased upon co-culture with dendritic cells (DCs) from IL-1RI−/− mice, while the responses were normal with DCs from IL-1α/β−/− mice. DTH responses in tumor necrosis factor α−/− (TNF−/−) mice were also suppressed; the magnitude of the suppression in IL-1α/β−/−TNF−/− mice, however, was similar to that observed in IL-1α/β−/− mice. These observations indicate that IL-1 possesses dual functions during the DTH response. IL-1β is necessary for the efficient priming of T cells. In addition, CD4+ T cell-derived IL-1 plays an important role in the activation of DCs during the elicitation phase, resulting in the production of TNF, that activate allergen-specific T cells.

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