IL- 21 and Immune Mediated Viral Control
IL-21 和免疫介导的病毒控制
基本信息
- 批准号:7802289
- 负责人:
- 金额:$ 47.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-01 至 2014-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAntibody FormationB-LymphocytesCD4 Positive T LymphocytesCD8B1 geneCellsChronicDefectDependencyDevelopmentGenerationsHelper-Inducer T-LymphocyteHeterogeneityHumanImmuneImmunityImmunologic MemoryInfectionInfection ControlLifeLongevityMediatingPlayRoleShapesSignal TransductionSourceT cell responseT memory cellT-LymphocyteT-Lymphocyte SubsetsTherapeuticTherapeutic EffectViralVirus Diseasesbasecombatexhaustionfunctional disabilityresponse
项目摘要
DESCRIPTION (provided by applicant): Developing an in-depth understanding of the factors that regulate the induction, quality, and longevity of anti- viral T cell responses is essential for devising rational strategies to combat viral infections. A hallmark of robust anti-viral immunity is the elaboration of potent CD4 and CD8 T cell responses which act cooperatively to bring about control of the infection. The consequences of ineffective responses can be catastrophic, resulting in viral persistence or the loss of long-lived immunological memory. Nevertheless, the signals which drive the development of the most robust polyfunctional effector responses and dictate the emergence of memory T cells are not fully understood. The purpose of this proposal is to capitalize on compelling preliminary findings which indicate that IL-21 plays a vital role in anti-viral immunity. Our initial studies clearly show that without sufficient levels of IL-21 the generation of polyfunctional effector CD8 T cells is compromised, and quite strikingly T cell exhaustion is exacerbated during chronic infections. Significantly, many of the phenotypic and functional impairments in anti-viral CDS T cells which manifest in the absence of IL-21 resemble the defects observed in CD4 T cell deficient hosts. A principal producer of IL-21 are CD4 follicular helper cells (Tfh) which function to help antibody responses, therefore Tfh derived IL-21 may be the critical factor that helps CD8 T cell responses. It is, however, unclear whether IL-21 is acting directly or indirectly on anti-viral CD8 T cells to promote their functionality, how T cell heterogeneity is shaped by IL-21, whether Tfh are the essential cellular sources of IL-21, and whether IL-21 based treatments have therapeutic benefits on viral control both during acute and chronic infection. We therefore propose the following specific aims: 1). Determine the direct effects of IL-21 on polyfunctional anti-viral CDS T cells. 2). Elucidate the role of CD4 T cell-derived IL-21 in promoting anti-viral immunity. 3). Define the significance of IL-21-producing CD4 T cells during viral infections of humans 4). Determine the therapeutic effects of IL-21 on anti-viral immunity and control.
描述(由申请人提供):对调节抗病毒T细胞反应的诱导,质量和寿命的因素进行深入了解对于制定合理策略以打击病毒感染是必不可少的。强大的抗病毒免疫的标志是对有效的CD4和CD8 T细胞反应的阐述,这些反应起着对感染的控制作用。无效反应的后果可能是灾难性的,导致病毒持久性或长期寿命的免疫记忆的丧失。然而,尚未完全了解驱动最强大的多功能效应子响应并决定记忆T细胞出现的信号。该提案的目的是利用引人注目的初步发现,表明IL-21在抗病毒免疫中起着至关重要的作用。我们的初步研究清楚地表明,如果没有足够水平的IL-21,多功能效应子CD8 T细胞的产生就会受到损害,并且在慢性感染过程中,T细胞的衰竭非常明显。值得注意的是,在没有IL-21的情况下表现出的抗病毒CDS T细胞中的许多表型和功能障碍类似于CD4 T细胞缺乏宿主中观察到的缺陷。 IL-21的主要生产子是CD4滤泡辅助细胞(TFH),其功能有助于抗体反应,因此衍生的IL-21可能是帮助CD8 T细胞反应的关键因素。但是,尚不清楚IL-21是直接或间接作用于抗病毒CD8 T细胞以促进其功能,T细胞异质性如何由IL-21塑造,是否是TFH是IL-21的必需细胞来源,是IL-21的必要细胞来源以及基于IL-21的治疗是否在急性和慢性感染期间对病毒控制具有治疗益处。因此,我们提出以下特定目标:1)。确定IL-21对多功能抗病毒CD T细胞的直接影响。 2)。阐明CD4 T细胞衍生的IL-21在促进抗病毒免疫中的作用。 3)。定义人类病毒感染期间产生IL-21的CD4 T细胞的重要性。确定IL-21对抗病毒免疫和控制的治疗作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Allan J Zajac其他文献
Allan J Zajac的其他文献
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{{ truncateString('Allan J Zajac', 18)}}的其他基金
The Regulation of T Cell Exhaustion by Adhesion Molecules
粘附分子对 T 细胞耗竭的调节
- 批准号:
8290753 - 财政年份:2012
- 资助金额:
$ 47.06万 - 项目类别:
The Regulation of T Cell Exhaustion by Adhesion Molecules
粘附分子对 T 细胞耗竭的调节
- 批准号:
8416362 - 财政年份:2012
- 资助金额:
$ 47.06万 - 项目类别:
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