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

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. © 2006 Oxford University Press.