International Immunology Advance Access originally published online on March 28, 2006
International Immunology 2006 18(5):701-712; doi:10.1093/intimm/dxl007
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IL-1ß, but not IL-1
, is required for antigen-specific T cell activation and the induction of local inflammation in the delayed-type hypersensitivity responses
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
1 Present address: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5176, USA
Correspondence to: Y. Iwakura; E-mail: iwakura{at}ims.u-tokyo.ac.jp
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-1ß-deficient (IL-1ß–/–) and IL-1
/ß–/– mice, but not in IL-1–/– mice. In contrast, responses in IL-1R antagonist–/– (IL-1Ra–/–) mice were exacerbated. Lymph node cells derived from mBSA-sensitized IL-1ß–/–, IL-1/ß–/– and IL-1R type I (IL-1RI)–/– mice, but not from IL-1–/– 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-1/ß–/– 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-1/ß–/–, 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-1/ß–/– mice. DTH responses in tumor necrosis factor –/– (TNF–/–) mice were also suppressed; the magnitude of the suppression in IL-1/ß–/–TNF–/– mice, however, was similar to that observed in IL-1/ß–/– mice. These observations indicate that IL-1 possesses dual functions during the DTH response. IL-1ß 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.
Keywords: allergy, cytokines, inflammation, knockout mice
Transmitting editor: K. Sugamura
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