The analysis of genes involved in the control of Th1/Th2 balance and its role in immune diseases

免疫系统对维持我们身体的内环境稳定以及神经和内分泌系统起着至关重要的作用。通常，我们的身体通过严格的免疫识别和免疫调节机制来保护免受各种疾病的侵害。然而，一旦发生免疫调节失衡，就会成为各种免疫性疾病的诱因。最近，已经阐明免疫平衡由两个辅助性T（Th）细胞亚群Th1和Th2调节。因此，研究Th1/Th2平衡在各种疾病中的作用，对于开发新的免疫性疾病诊断和治疗方法具有重要意义。本文主要探讨Th1/Th2平衡的调控机制及其在免疫性疾病中的作用。此外，我们还对影响Th1/Th2平衡的遗传因素进行了研究，以明确遗传性免疫疾病的相关因素。我们利用抗原特异性Th1和Th2细胞建立了肿瘤、变态反应和肝损伤的新动物模型。实验结果表明，来源于同一原始Th细胞的Th1和Th2细胞在体内疾病发病过程中发挥着完全不同的作用.特应性皮炎（AD）患者存在Th1/Th2平衡异常。从AD患者中获得的CD4 + T细胞显示IFN-γ产生能力降低。进一步阐明了PPD反应性CD4 + CD45RO+记忆T细胞的定量和定性缺陷.将参与控制Th1/Th2平衡的基因定位在小鼠染色体上。其中一个候选基因位于IL-4受体α基因附近，与特应性皮炎的发生有关。

Immune system plays a critical role for maintaining the homeostasis of our body as well as nervous and endocrine systems. Generally, our body is protected from various diseases by a strict immunorecognition and immunoregulation mechanisms. However, once, the imbalance of immunoregulation is occurred, it becomes causes of various immune diseases. Recently, it has been clarified that immune balance is regulated by two helper T (Th) cell subsets, Th1 and Th2. Therefore, it is a great important issue to investigate the role of Th1/Th2 balance in various diseases to develop new diagnosis and treatment for immune diseases. Here, we investigated the control mechanisms of Th1/Th2 balance and its role in immune diseases. Moreover, we also pursued factors involved in genetically controlled Th1/Th2 balance to make clear the factors related to genetic immune diseases.As results, we demonstrated new findings as described in the following ;1. We esiablished new animal models for tumor, allergy and liver injury using antigen-specific Th1 and Th2 cells. It was demonstrated that Th1 and Th2 cells derived from the same naive Th cells exhibited totally distinct role during the onset of diseases in vivo.2. The abnormality of Th1/Th2 balance in atopic dermatitis (AD) patients was demonstrated. CD4+T cells obtained from AD patients revealed reduced IFN-g producing ability. Moreover, quantitative and qualitative defect of CD4+CD45RO+ memory T cells reactive against PPD was clarified.3. The genes involved in the control of Th1/Th2 balance was mapped on mouse chromosomes. One of the candidate genes was located nearby IL-4 receptor a gene, which is related to the incidence of atopic dermatis.