NUCLEAR TRANSCRIPTION FACTOR ROLE IN T CELL ACTIVATION AND DISEASE

核转录因子NF- B（如p52）家族和I B（如p52）家族是核转录因子家族的重要成员。 Bcl-3）家族，在细胞的反应中起关键作用， 免疫系统 这些蛋白质的体外活性已经过检测 但它们在体内的作用尚未有文献记载。 Bcl-3缺陷小鼠 和p52，以解决这些的体内功能， proteins. Bcl-3缺陷和p52缺陷小鼠均表现出 重叠的表型，因为他们有缺陷的脾 微结构、生发中心反应和体液反应。 在 同时也各自展现出一些独特的特点。 这些 这些发现证明了这些蛋白质的体内功能，特别是 关于B细胞功能。 这个小组评估造血重建的方案， 接受化疗的患者中的淋巴样谱系细胞。 一 重建的主要障碍来自移植物抗宿主病， 存在于供体移植物中的T细胞对受体起反应。 我们 还评估了设计用于治疗自身攻击性免疫 多发性硬化症和关节炎等疾病。 在这些疾病中， 病理是由炎症免疫反应和电流介导的 治疗这些疾病的策略是针对抑制 这些炎症反应。 了解细胞内 这些反应的介质和动物模型的创建， 反映这些过程，如本项目中使用的过程， 用于开发和测试新疗法。 此外，这项研究 需要深入了解免疫荧光，流式细胞术， 细胞因子测定，申办者用于评估其 产品和临床前/临床结果。

Nuclear transcription factors, NF- B (e.g. p52) family and I B (e.g. Bcl-3) family, play a critical role in the response of cells of the immune system. The in vitro activity of these proteins has been examined but their in vivo role had not been documented. Mice deficient in Bcl-3 and p52 were generated in order to address the vivo function of these proteins. Both Bcl-3-deficient and p52-deficient mice exhibited overlapping phenotypes in that they had defects in splenic microarchitecture, germinal center reactions, and humoral responses. At the same time, they each exhibited some unique characteristics. These finding demonstrate an in vivo function for these proteins, particularly in regard to B cell function. This group evaluates protocols for the reconstitution of hematopoietic and lymphoid lineage cells in patients who have received chemotherapy. A major impediment to reconstitution comes from graft vs host disease, in which T cells present in the donor graft react against the recipient. We also assess protocols designed for the treatment of autoaggressive immune diseases such as multiple sclerosis and arthritis. In these diseases, pathology is mediated by inflammatory immune responses and current strategies for the treatment of these diseases is directed at suppressing these inflammatory responses. An understanding of the intracellular mediators of these responses and the creation of animal models that reflect these processes, such as those used in this project, are essential for the development and testing of new therapies. Moreover, this research require an in depth knowledge of immunfluorescence, flow cytometry, and cytokine assays, techniques which are used by sponsors to assess their products and preclinical/clinical results.