Search for transcriptional factor which regulates helper T cell Th1/Th2 balance.

刘易斯大鼠倾向于辅助性T细胞（Th）1免疫应答，而布朗挪威（BN）大鼠对Th 2免疫应答敏感。然而，这两种菌株之间不同结果的诱导的精确机制仍然难以捉摸。我们研究了刘易斯和BN大鼠中负责抗原特异性免疫应答极化为占优势的Th 1或Th 2型的一些细胞因子及其受体和辅助分子的表达水平。我们观察到这些品系之间IL-12 p40表达的明显差异，其在刘易斯大鼠的淋巴结细胞中较高。IL-12受体β1、β2、IFN-γ受体α和β基因表达的上调在刘易斯大鼠比BN大鼠更显著。因此，巨噬细胞或树突状细胞产生IL-12似乎是Th 1细胞活化的必要事件。为了了解刘易斯大鼠Th 1细胞活化的机制，我们研究了抗原呈递过程。12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）诱导人单核细胞白血病THP-1细胞分化为巨噬细胞样细胞。在这个过程中。IFN-γ诱导的HLA-DRα表达明显增强。HLA-DRα表达的增强至少是由于TPA依赖的IFN-γ受体基因的诱导。本研究对TPA诱导IFN-γ R1基因表达上调的机制进行了研究，并鉴定了IFN-γ R1基因启动子中的TPA反应元件。

Lewis rats are prone to T helper (Th)1 immune responses, whereas Brown Norway (BN) rats are susceptible to Th2 immune responses. Yet, the precise mechanism of induction of the different outcome between these two strains remained elusive. We investigated the expression levels of some cytokines, their receptors and accessory molecules, responsible for the polarization of antigen-specific immune response into a predominant Th1 or Th2 profile in Lewis and BN rats. We observed clear differences between these strains in the expression of IL-12p40, which was high in lymph node cells of Lewis rats. Upregulation of the expression of IL-12 receptor β1, β2, IFN-γ receptor α and β genes were more prominent in Lewis rats rather than BN rats. Thus, IL-12 production by macrophages or dendritic cells seems to be essential event for the activation of Th1 cellsTo understand the mechanism of Th1 activaion in Lewis rats, we investigates process of antigen-presentation. Human monocytic leukemia THP-1 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA). During this process. IFN-γ-inducible expression of HLA-DRα is markedly enhanced. The enhancement of HLA-DRα expression is at least due to the TPA-dependent induction of the IFN-γ receptor genes. We have studied the mechanism of TPA-induced up-regulation of the IFN-γ R1 gene and identified TPA-responsive element in the promoter of IFN-γ receptor gene.