Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Eur J Immunol. 2011 Nov;41(11):3351-60. doi: 10.1002/eji.201141629. Epub 2011 Oct 13.
The effector functions of CD8(+) T cells are influenced by tissue inflammatory microenvironments. IL-33, a member of the IL-1 family, acts as a danger signal after its release during cell necrosis. The IL-33/ST2 axis has been implicated in various Th2 responses. Its role in CD8(+) T-cell-mediated immune response is, however, not known. Here we find that type 1 cytotoxic T (Tc1) cells cultured in vitro unexpectedly express high levels of the IL-33 receptor ST2. Interestingly, the expression of ST2 in Tc1 cells is dependent on T-bet, a master Th1/Tc1 transcription factor. In addition, IL-33 enhances TCR-triggered IFN-γ production. IL-33 together with IL-12 can stimulate IFN-γ production in Tc1 cells. Moreover, IL-33 synergizes with IL-12 to promote CD8(+) T-cell effector function. The synergistic effect of IL-33 and IL-12 is partly mediated by Gadd45b. Together, these in vitro data establish a novel role of IL-33 in promoting effector type 1 adaptive immune responses.
CD8(+)T 细胞的效应功能受组织炎症微环境的影响。IL-33 是 IL-1 家族的一员，在细胞坏死过程中释放后充当危险信号。IL-33/ST2 轴与各种 Th2 反应有关。然而，其在 CD8(+)T 细胞介导的免疫反应中的作用尚不清楚。在这里，我们发现体外培养的 1 型细胞毒性 T（Tc1）细胞出乎意料地表达高水平的 IL-33 受体 ST2。有趣的是，Tc1 细胞中 ST2 的表达依赖于 T-bet，这是一种 Th1/Tc1 转录因子。此外，IL-33 增强 TCR 触发的 IFN-γ 产生。IL-33 与 IL-12 一起可以刺激 Tc1 细胞产生 IFN-γ。此外，IL-33 与 IL-12 协同促进 CD8(+)T 细胞效应功能。IL-33 和 IL-12 的协同作用部分是通过 Gadd45b 介导的。综上所述，这些体外数据确立了 IL-33 在促进效应型 1 适应性免疫反应中的新作用。
