Nam Kyung-Ok, Shin Su-Mi, Lee Hyeon-Woo
The Immunomodulation Research Center and Graduate Program in Immunology and Biomedicine, University of Ulsan, Ulsan 680-749, South Korea.
Cytokine. 2006 Jan 21;33(2):87-94. doi: 10.1016/j.cyto.2005.12.003. Epub 2006 Feb 20.
4-1BB, one of co-stimulatory molecules, is a member of TNF receptor superfamily and expressed on T cells upon TCR ligation. We have shown that 4-1BB is a co-stimulatory molecule enhancing cell cycle progression and inhibiting activation-induced cell death of CD8+ T cells by enhancing TCR signaling pathways. Here, we first report that the cross-linking of 4-1BB increased the expression of IL-13 mRNA and protein, and its secretion apparently via calcineurin, a Ca2+/calmodulin-dependent phosphatase. Ligation of 4-1BB with p815-m-4-1BBL evoked intracellular Ca2+ level in CD8+ T cells. CD8+ T cells express IL-13 receptor alpha1 mRNA. Incubation with anti-IL-13 blocking mAb reduced proliferation of CD8+ T cells enhanced by 4-1BB, and the treatment of CD3/4-1BB-ligated CD8+ T cells with recombinant IL-13 enhances cell proliferation, indicating that 4-1BB-induced IL-13 expression is partially responsible for the CD8+ T cell expansion in an autocrine or paracrine manner.
共刺激分子之一的4-1BB是肿瘤坏死因子受体超家族的成员，在TCR连接后表达于T细胞上。我们已经表明，4-1BB是一种共刺激分子，可通过增强TCR信号通路来促进细胞周期进程并抑制CD8+T细胞的激活诱导性细胞死亡。在此，我们首次报道，4-1BB的交联增加了IL-13 mRNA和蛋白的表达，并且其分泌显然是通过钙调神经磷酸酶（一种Ca2+/钙调蛋白依赖性磷酸酶）实现的。用p815-m-4-1BBL连接4-1BB可引起CD8+T细胞内Ca2+水平升高。CD8+T细胞表达IL-13受体α1 mRNA。用抗IL-13阻断单克隆抗体孵育可降低由4-1BB增强的CD8+T细胞的增殖，而用重组IL-13处理CD3/4-1BB连接的CD8+T细胞可增强细胞增殖，这表明4-1BB诱导的IL-13表达以自分泌或旁分泌方式部分地促成了CD8+T细胞的扩增。
