Role of Gamma/Delta T Cells in West Nile Virus Pathogenesis
Role of Gamma/Delta T Cells in West Nile Virus Pathogenesis
批准号:
8339444
负责人:
Tian Wang
金额:
$7.65万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-09-30 至 2014-08-31
关键词:
AntibodiesBrain InjuriesDataDevelopmentDisease OutbreaksEncephalitisExhibitsGoalsImmuneImmune responseImmunityInfectionInterferonsInvestigationLeadMediatingMusNorth AmericaPathologyPopulationPredispositionPublic HealthRegulationRoleStagingT-LymphocyteT-Lymphocyte SubsetsViral EncephalitisViral PathogenesisVirus DiseasesWest Nile virusagedbasenervous system disorderpathogenpreventresponsevectorvirus pathogenesis
中文摘要
描述(由申请人提供):西尼罗病毒(WNV)引起的神经系统疾病已成为北美日益关注的公共卫生问题。尽管对西尼罗河病毒的免疫反应一直是深入研究的主题,但免疫介导的病理在西尼罗河病毒诱导的神经系统疾病中的作用尚不完全清楚。我们的长期目标是了解西尼罗河病毒的发病机制。在这个提案中,我们将重点讨论一个具体的角色??T细胞亚型,即V?4+ T细胞在西尼罗河病毒脑炎中的作用。我们之前已经证明了??T细胞,非经典T细胞群,对西尼罗河病毒传播的早期控制很重要。在进一步调查??T细胞亚群在西尼罗河病毒感染中,我们发现V?1+ T细胞增强宿主易感性;而V??+ T细胞降低宿主易感性。脾V ?1+ T细胞在西尼罗河病毒感染的早期急剧扩增,并产生大量的IFN-?这些数据使我们认为它在保护性免疫中起作用。相反,V?4+ T细胞对感染的反应是适度扩张。此外,我们的数据显示,老年小鼠比年轻小鼠更容易感染西尼罗河病毒。老年小鼠对V?1+ T细胞,同时保持较高的V??4+ T细胞在感染早期。基于这些事实,我们假设V??4+ T细胞参与了西尼罗河病毒发病机制的调控。在Specific Aim1中,我们将进一步研究V??的致病作用。4+ T细胞在西尼罗河病毒感染期间。在具体目标2中,我们将尝试理解V??4+ T细胞在西尼罗河病毒感染期间调节宿主免疫。西尼罗河病毒现已引起北美最大的病毒性脑炎暴发,并已成为一个公共卫生问题。本研究结果将有助于加深我们对病毒发病机制的理解;它们还将导致制定预防和治疗西尼罗河病毒引起的脑炎的新战略。
英文摘要
DESCRIPTION (provided by applicant): West Nile virus (WNV)-induced neurological disease has become an increasing public health concern in North America. Although immune responses to WNV have been the subject of intense investigation, the role of immune-mediated pathology in WNV-induced neurological diseases is incompletely understood. Our long- term goal is to understand the mechanism of WNV pathogenesis. In this proposal, we will focus on the role of one specific ?? T cell subtype- namely V?4+ T cells in WNV-induced encephalitis. We have previously shown that ?? T cells, the non-classical T cell population, are important for early control of WNV dissemination. In further investigation of the role of ?? T cell subsets in WNV infection, we have found that antibody depletion of V?1+ T cells enhances host susceptibility; while depletion of V??? + T cells reduces host susceptibility. Splenic V?1+ T cells expand dramatically at the early stage of WNV infection and produce significant amounts of IFN-?, data which lead us to suggest a role in protective immunity. In contrast, V?4+ T cells expand modestly in response to infection. Moreover, our data show that the aged mice are more susceptible to WNV infection than are young mice. Aged mice exhibit a slower and reduced response by V?1+ T cells, while maintaining a higher number of V??4+ T cells at the early stage of infection. Based on these facts, we hypothesize that V??4+ T cells are involved in the regulation of WNV pathogenesis. In Specific Aim1, we will further investigate the pathogenic effect of V??4+ T cells during WNV infection. In Specific Aim 2, we will attempt to understand the mechanisms by which V??4+ T cells regulate host immunity during WNV infection. WNV has now induced the largest outbreaks of viral encephalitis in North America and has become a public health concern. Results from this study will help to enhance our understanding of viral pathogenesis; they will also lead to the development of new strategies to prevent and treat WNV-induced encephalitis.
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