IL-1beta, but not IL-1alpha, is required for antigen-specific T cell activation and the induction of local inflammation in the delayed-type hypersensitivity responses.
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-1beta-deficient (IL-1beta-/-) and IL-1alpha/beta-/- mice, but not in IL-1alpha-/- mice. In contrast, responses in IL-1R antagonist-/- (IL-1Ra-/-) mice were exacerbated. Lymph node cells derived from mBSA-sensitized IL-1beta-/-, IL-1alpha/beta-/- and IL-1R type I (IL-1RI)-/- mice, but not from IL-1alpha-/- 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-1alpha/beta-/- 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-1alpha/beta-/-, 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-1alpha/beta-/- mice. DTH responses in tumor necrosis factor alpha-/- (TNF-/-) mice were also suppressed; the magnitude of the suppression in IL-1alpha/beta-/-TNF-/- mice, however, was similar to that observed in IL-1alpha/beta-/- mice. These observations indicate that IL-1 possesses dual functions during the DTH response. IL-1beta 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.
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Tokyo 108-8639, Japan.
Aya
A
Nambu
Susumu
S
Nakae
Yoichiro
Y
Iwakura
D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000172:deficiency / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma