Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2012 Aug 1;189(3):1400-5. doi: 10.4049/jimmunol.1200491. Epub 2012 Jun 27.
An effective immune response to Ag challenge is critically dependent on the size of the effector cell population generated from clonal activation of Ag-specific T cells. The transcription network involved in regulating the size of the effector population, particularly for CD4 Th cells, is poorly understood. In this study, we investigate the role of Id2, an inhibitor of E protein transcription factors, in the generation of CD4 effectors. Using a T cell-specific conditional Id2 knockout mouse model, we show that inhibitor of DNA binding (Id)2 is essential for the development of experimental autoimmune encephalomyelitis. Although Ag-specific and IL-17-producing CD4 T cells are produced in these mice, the activated CD4 T cells form a smaller pool of effector cells in the peripheral lymphoid organs, exhibit reduced proliferation and increased cell death, and are largely absent in the CNS. In the absence of Id2, E protein targets, including the proapoptotic protein Bim and SOCS3, are expressed at higher levels among activated CD4 T cells. This study reveals a critical role of Id2 in the control of effector CD4 T cell population size and the development of a Th17-mediated autoimmune disease.
针对 Ag 挑战的有效免疫反应极大地依赖于 Ag 特异性 T 细胞克隆激活产生的效应细胞群体的大小。涉及调节效应群体大小的转录网络，特别是对于 CD4 Th 细胞，目前了解甚少。在这项研究中，我们研究了 Id2（一种 E 蛋白转录因子的抑制剂）在 CD4 效应细胞产生中的作用。使用 T 细胞特异性条件性 Id2 敲除小鼠模型，我们表明抑制 DNA 结合（Id）2 对于实验性自身免疫性脑脊髓炎的发展是必需的。尽管在这些小鼠中产生了 Ag 特异性和产生 IL-17 的 CD4 T 细胞，但活化的 CD4 T 细胞在周围淋巴器官中形成更小的效应细胞池，表现出增殖减少和细胞死亡增加，并且在中枢神经系统中基本上不存在。在缺乏 Id2 的情况下，活化的 CD4 T 细胞中表达更高水平的 E 蛋白靶标，包括促凋亡蛋白 Bim 和 SOCS3。这项研究揭示了 Id2 在控制效应 CD4 T 细胞群体大小和 Th17 介导的自身免疫疾病发展中的关键作用。
