繆希椿2018-07-092018-07-092005http://ntur.lib.ntu.edu.tw//handle/246246/25375初生的CD4 + T 淋巴細胞在T 細胞受體接受訊號後，會分化為兩個不同的族 群：Th1 和Th2 細胞。成熟的Th 作用淋巴細胞在免疫系統中扮演協調的角色。 Th1 細胞產生干擾素γ 、介白素二及淋巴毒素，媒介了延遲性過敏反應和巨嗜細 胞的活化。Th1 免疫反應在對抗細胞內病原與媒介器官特異性自體免疫上很重 要。相對的，Th2 細胞產生介白素四、五、六、九、十及十三，並媒介B 細胞產 生抗體。Th2 免疫反應在對抗蠕蟲及發炎反應上扮演決定性的角色。 最 近的研究顯示T 淋巴細胞特異的轉錄因子：T-bet 、GATA3 與c-MAF 在 Th1/Th2 的發育上是必需的。T-bet 是Th1 細胞分化的主要調控者，然而GATA3 與c-MAF 則在Th2 的發育上扮演決定性的角色。其它因子，如細胞激素、多肽媒 介者Eta-1 、化學激素MCP-1 、訊息傳導及活化者4(STAT4)及STAT6 也會影響T 細胞的分化。然而許多實驗指出，一些其他未被確定的因子也參與T 細胞的分 化。所以，我們計畫有效率的篩選和辨識這些參與T 細胞分化的因子(實驗目標 一)，並在體內及體外模式中研究他們在Th1/Th2 的發育與免疫反應中的角色(實 驗目標二及三)。 這 個計畫的目標是希望能在分子與細胞機轉上，對基因如何調節T 細胞 分化與免疫反應有進一步的了解。此外，我們也希望建立Th1 或Th2 免疫系統小 鼠模式，以提供對Th1 疾病(如器官特異性自體免疫)或Th2 疾病(如氣喘和過敏) 更好的了解與控制。Naïve CD4 + T lymphocytes differentiate into two distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), upon T cell receptor engagement. Mature effectors Th lymphocyte plays an orchestrated role in the immune system. Th1 cells produce IFN摯瑬敳獩 , IL2 and lymphotoxin, and mediate responses of delayed-type hypersensitivity and activation of macrophage. Th1 responses are important for protection against intracellular pathogens and mediate organ-specific autoreactive immune responses. Conversely, Th2 cells produce IL4, IL5, IL6, IL9, IL10 and IL13, and mediate antibody production by B cells. Th2 responses are critical in protection against helminths and responsible for anti-inflammatory reactions. Recent studies have shown that T lymphocyte specific transcription factors T-bet, GATA3 and c-MAF have essential roles in the Th1/Th2 development. T-bet is the master regulator for the development of the Th1 cell lineage, while GATA3 and c-MAF are crucial for the development of the Th2 cell lineage. Other factors, such as cytokines, polypeptide mediator Eta1, chemokine MCP-1, signal transducer and activator of transcription 4 (STAT4), and STAT6 also influence the T lymphocyte differentiation. However, many studies indicate that some other factors involved in Th differentiation are yet to be identified. Therefore, we intend to effectively screen and identify the factors crucial for T lymphocyte differentiation (Specific Aim 1) and study their roles in Th1/Th2 and immune response in vitro and in vivo (Specific Aim 2&3). The goal of this proposal is to provide a better insight of the molecular and cellular mechanisms by which genes regulate T Lymphocyte differentiation and immune response. Furthermore, we hope to establish the Th1/Th2-skewed mouse models for better understanding and controlling of Th1-mediated diseases, such as organ-specific autoimmunity diseases and Th2-mediated diseases, such as asthma and allergy.application/pdf125537 bytesapplication/pdfzh-TW國立臺灣大學醫學院免疫學研究所T 淋巴細胞基因調控及免疫反應T LymphocyteGene RegulationImmune Responsejournal articlehttp://ntur.lib.ntu.edu.tw/bitstream/246246/25375/1/932320B002078.pdf