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

刘易斯大鼠容易产生T辅助细胞(Th)1免疫反应，而布朗挪威(BN)大鼠容易产生Th2免疫反应。然而，这两个菌株之间不同结果的确切诱导机制仍然不清楚。我们研究了一些细胞因子及其受体和辅助分子的表达水平，这些细胞因子负责在Lewis和BN大鼠中将抗原特异性免疫反应极化为主要的Th1或Th2类型。我们观察到这些菌株在IL-12p40的表达上有明显的差异，IL-12p40在Lewis大鼠的淋巴结细胞中是高表达的。IL-12受体β1、β2、γ受体α和β基因表达上调在Lewis大鼠较BN大鼠更为显著。因此，巨噬细胞或树突状细胞产生IL-12似乎是Th1细胞激活的重要事件。为了了解Lewis大鼠Th1激活的机制，我们研究了抗原提呈过程。人单核细胞白血病THP-1细胞在12-O-十四烷基佛波酯(TPA)作用下可分化为巨噬细胞样细胞。在这个过程中。干扰素-γ诱导的人类白细胞抗原-DRα表达明显增强。HLADRα表达的增强至少是由于TPA依赖的干扰素-γ受体基因的诱导。我们已经研究了TPA诱导干扰素-γ受体基因上调的机制，并在干扰素-γ受体基因的启动子中发现了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.