The impact of IL-4 on the CD8 T cell response to pathogens

IL-4对CD8 T细胞对病原体反应的影响

• 批准号: 8293998
• 负责人: STEPHEN C JAMESON
• 金额: $ 22.8万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8293998
• 关键词: Address; Allergic; Antigens; Automobile Driving; Bacteria; Biological Models; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Cytokine Signaling; Data; Development; Disease; Health; Human; Immune response; Immunity; Infection; Infection Control; Interferons; Interleukin-13; Interleukin-2; Interleukin-4; Lead; Listeria; Listeria monocytogenes; Maintenance; Malaria; Mediating; Memory; Mus; Parasites; Phenotype; Plasmodium; Play; Production; Proteins; Publishing; Resistance; Resolution; Role; Serum Proteins; Signal Transduction; T cell response; T-Cell Proliferation; T-Lymphocyte; Testing; Vaccines; Virus; Work; base; clinically relevant; cytokine; cytokine therapy; improved; innovation; interest; interleukin-13 receptor; novel; pathogen; prevent; receptor; response

DESCRIPTION (provided by applicant): The cytokine IL-4 is well studied for its role in driving allergic/asthmatic CD4 T cell responses: However its impact on CD8 T cells is much less clear. Building on published and preliminary data, we propose that IL-4 plays a critical and unexpected role in supporting the CD8 T cell response to pathogens. These findings will be investigated further to define the exact role of IL-4 responsiveness in the CD8 T cell response, and additional work will test the novel concept that IL-4 cytokine therapy could be used to enhance CD8 T cell protective immunity against malarial parasites. PUBLIC HEALTH RELEVANCE: Many infections are controlled by "killer" T lymphocytes (CTL), and there is a pressing need to improve vaccines that produce these cells. Here we look at an unexpected and interesting role for a serum protein called IL-4 which, based on our preliminary data, is critical to achieve a strong CTL response against infection. We test the role of IL-4 in the CTL responses against two pathogens (Listeria bacteria and malaria parasites) to establish what IL-4 does in controlling CTL responses (Aim 1) and test how this protein can be used to enhance CTL activity in order to prevent malarial disease.

描述（由申请人提供）：细胞因子 IL-4 因其在驱动过敏/哮喘 CD4 T 细胞反应中的作用而得到充分研究：然而，其对 CD8 T 细胞的影响尚不清楚。基于已发表的初步数据，我们提出 IL-4 在支持 CD8 T 细胞对病原体的反应中发挥着关键且意想不到的作用。这些发现将进一步研究，以确定 IL-4 反应性在 CD8 T 细胞反应中的确切作用，并且额外的工作将测试 IL-4 细胞因子疗法可用于增强 CD8 T 细胞针对疟疾寄生虫的保护性免疫的新概念。 公共卫生相关性：许多感染是由“杀手”T 淋巴细胞 (CTL) 控制的，因此迫切需要改进产生这些细胞的疫苗。在这里，我们研究了一种名为 IL-4 的血清蛋白的意想不到且有趣的作用，根据我们的初步数据，它对于实现针对感染的强大 CTL 反应至关重要。我们测试了 IL-4 在针对两种病原体（李斯特菌和疟原虫）的 CTL 反应中的作用，以确定 IL-4 在控制 CTL 反应中的作用（目标 1），并测试如何使用该蛋白来增强 CTL 活性以预防疟疾。