MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 6536047
• 负责人: Alejandro V Villarino
• 金额: $ 3.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6536047
• 关键词: CD28 molecule; T lymphocyte; Toxoplasma gondii; biological signal transduction; genetically modified animals; interferon gamma; interleukin 12; laboratory mouse; microorganism immunology; natural killer cells; nuclear factor kappa beta; protein biosynthesis; toxoplasmosis

Toxoplasma gondii is an important parasitic infection causing much morbidity and mortality in patients with primary or acquired immunodeficiencies. Because production of IFNg is crucial in both innate and adaptive immunity to toxoplasmosis, understanding the molecular mechanisms involved in the induction of this cytokine will be paramount to developing novel treatment strategies. The transcription factor NF-kB has been implicated in the production of IFNg by both NK and T cells; principal mediators of innate and adaptive immunity to toxoplasmosis respectively. Using retroviral gene transfection to selectively inhibit NF-kB signaling, it will be possible to assess the role of this transcription factor in the production of IFNg by NK cells in vitro. In addition, by reconstituting sublethally irradiated RAG -/- mice with these virally transfected cells, the importance of NF-kB signaling in innate immunity to toxoplasmosis can be determined in vivo. Furthermore, by employing a transgenic mouse model in which NF-kB signaling is inhibited in T cells, the role of NF-kB activation in T cell mediated resistance to T. gondii infection can be determined.

弓形虫Gondii是一种重要的寄生虫感染，导致原发性或获得性免疫缺陷患者的发病率和死亡率很大。 由于IFNG的产生在对毒质剂的先天和适应性免疫方面至关重要，因此了解诱导这种细胞因子所涉及的分子机制对于制定新型治疗策略至关重要。 NK和T细胞都与转录因子NF-KB有关IFNG的产生。先天性和适应性免疫对弓形虫病的主要介体。 使用逆转录病毒基因转染有选择地抑制NF-KB信号传导，可以评估该转录因子在体外NK细胞产生IFNG中的作用。 此外，通过与这些病毒转染的细胞重构辐照的抹布 - / - 小鼠，可以在体内确定NF-KB信号在先天免疫对毒质剂中的免疫中的重要性。 此外，通过采用转基因小鼠模型，在T细胞中抑制了NF-KB信号传导，可以确定NF-KB激活在T细胞中介导的T. gondii感染的抗性中的作用。