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

描述(申请人提供)：细胞因子IL-4因其在驱动过敏/哮喘的CD4T细胞反应中的作用而得到很好的研究：然而，它对CD8T细胞的影响还不是很清楚。基于已发表的和初步的数据，我们认为IL-4在支持CD8T细胞对病原体的反应中发挥着关键和意想不到的作用。这些发现将被进一步研究，以确定IL-4应答在CD8 T细胞应答中的确切作用，进一步的工作将检验IL-4细胞因子疗法可用于增强CD8 T细胞对疟疾寄生虫的保护性免疫这一新概念。 与公共卫生相关：许多感染是由“杀手”T淋巴细胞(CTL)控制的，迫切需要改进生产这些细胞的疫苗。在这里，我们看到了一种名为IL-4的血清蛋白的一个意想不到和有趣的作用，根据我们的初步数据，它是实现针对感染的强大CTL反应的关键。我们测试IL-4在针对两种病原体(李斯特氏菌和疟疾寄生虫)的CTL反应中的作用，以确定IL-4在控制CTL反应中所起的作用(目标1)，并测试该蛋白如何用于增强CTL活性以预防疟疾。

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.