Yoo Jae Kwang, Cho Jae Ho, Lee Seung Woo, Sung Young Chul
National Laboratory of DNA Medicine, Division of Molecular and Life Science, Pohang University of Science and Technology, Hyoja Dong, Pohang, Korea.
J Immunol. 2002 Oct 1;169(7):3637-43. doi: 10.4049/jimmunol.169.7.3637.
IL-12 is a pleiotropic cytokine that plays an important role in innate and adaptive immunity. IL-12 induces T cell proliferation and IFN-gamma secretion from activated T cells. It was also reported that IL-12 prevents apoptosis of CD4(+) T cells. However, the signaling mechanism that regulates these IL-12-induced responses is poorly understood yet. In this study, we demonstrated that IL-12 activates phosphatidylinositol 3-kinase (PI3K)/Akt pathway in murine CD4(+) T cells, and that this signaling pathway is required for IL-12-induced T cell proliferation and antiapoptotic function, but not for IFN-gamma induction. Through PI3K/Akt pathway, IL-12 up-regulates the expression of cell cycle-related molecule such as cyclin D3, and antiapoptotic molecules such as Bcl-2 and cellular inhibitors of apoptosis proteins-2, followed by down-regulation of active caspase-3. These results suggest that PI3K/Akt pathway is critical for mediating IL-12-induced CD4(+) T cell responses such as T cell proliferation and survival.
白细胞介素-12（IL-12）是一种多效性细胞因子，在固有免疫和适应性免疫中发挥重要作用。IL-12可诱导T细胞增殖以及活化T细胞分泌γ干扰素（IFN-γ）。也有报道称IL-12可防止CD4(+) T细胞凋亡。然而，调节这些IL-12诱导反应的信号传导机制目前仍知之甚少。在本研究中，我们证明IL-12可激活小鼠CD4(+) T细胞中的磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路，并且该信号通路对于IL-12诱导的T细胞增殖和抗凋亡功能是必需的，但对于IFN-γ的诱导并非必需。通过PI3K/Akt信号通路，IL-12上调细胞周期相关分子如细胞周期蛋白D3的表达，以及抗凋亡分子如Bcl-2和凋亡蛋白抑制因子-2的表达，随后下调活化的半胱天冬酶-3。这些结果表明，PI3K/Akt信号通路对于介导IL-12诱导的CD4(+) T细胞反应如T细胞增殖和存活至关重要。
