CNS-Specific Regulatory CD8+ T Cells in Autoimmune Demyelination
CNS 特异性调节 CD8 T 细胞在自身免疫性脱髓鞘中的作用
基本信息
- 批准号:8627103
- 负责人:
- 金额:$ 31.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-05-01 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS). A great deal of our understanding about the immunologic processes that underlie MS derives from studies in its autoimmune animal model, experimental autoimmune encephalomyelitis (EAE). However, the vast majority of studies in EAE and MS have focused on evaluating and targeting CD4+ T cell responses, with the general assumption that these diseases are predominantly Th1/Th17-mediated and Th2/Treg-modulated. Recent reports from others and us indicate that CD8+ T cells may play an important role in the pathogenesis as well as regulation of autoimmune demyelination. The role of CD8+ T cells in the process of autoimmune pathology has been both understudied and controversial. While it is known that CD8+ T cells represent the predominant T cell in an MS lesion and are oligoclonally expanded at the site of pathology, the antigenic specificity of these cells and their role is not known. There is high prevalence of CNS-specific CD8+ T cells in MS patients as well as multiple models of EAE. While it makes intuitive sense that a CNS-targeted, MHC Class I-restricted CD8+ T cell response would likely have a pathogenic role in disease, our recent studies have generated the first evidence for a novel and unexpected immune suppressor role for neuroantigen-specific CD8+ T cells in EAE. We thus hypothesize that CNS-specific CD8+ T cells form an important arm of intrinsic immune regulation during autoimmune demyelinating disease. We propose that this natural process can be harnessed for the development of an effective immunotherapeutic strategy. The experiments proposed in this application will directly address the mechanisms of immune modulation by CNS-reactive CD8+ T cells, delineating their cellular, molecular and trafficking requirements. Moreover, the most potent immune suppressive subset of this population will be defined with the goal of developing a novel immunotherapeutic approach. We believe that the proposed experiments will provide greater fundamental insight into CD8+ T cell-mediated immune regulation during health and disease and will pave the way for newer intervention strategies for this and other immune-mediated diseases.
描述(由申请人提供):多发性硬化症(MS)是中枢神经系统(CNS)的炎症性脱髓鞘疾病。我们对MS基础的免疫过程的了解,这是我们自身免疫动物模型中的研究,实验性自身免疫性脑脊髓炎(EAE)。然而,EAE和MS的绝大多数研究都集中在评估和靶向CD4+ T细胞反应上,并且通常假设这些疾病主要是TH1/TH17介导的,并且Th2/Treg调节。来自其他人和美国的最新报告表明,CD8+ T细胞在发病机理以及自身免疫性脱髓鞘的调节中可能起重要作用。 CD8+ T细胞在自身免疫性病理学过程中的作用既研究又有争议。虽然众所周知,CD8+ T细胞代表MS病变中主要的T细胞,并且在病理部位旨在寡聚,但这些细胞的抗原特异性及其作用尚不清楚。 MS患者以及EAE多种模型中,CNS特异性CD8+ T细胞患病率很高。虽然具有直觉的意义,即具有CNS的MHC I限制的CD8+ T细胞反应可能在疾病中具有致病作用,但我们最近的研究为EAE中神经抗原特异性CD8+ T细胞产生了新型和意外的免疫抑制作用作用的证据。因此,我们假设CNS特异性CD8+ T细胞在自身免疫性脱髓鞘疾病期间形成了内在免疫调节的重要组件。我们建议可以利用这种自然过程来制定有效的免疫治疗策略。本应用中提出的实验将直接解决CNS反应性CD8+ T细胞免疫调节的机制,从而描述其细胞,分子和运输要求。此外,该人群中最有效的免疫抑制子集将以开发一种新型的免疫治疗方法来定义。我们认为,拟议的实验将为健康和疾病期间的CD8+ T细胞介导的免疫调节提供更大的基本见解,并为这种和其他免疫介导的疾病铺平道路。
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)
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数据更新时间:2024-06-01
NITIN J KARANDIKAR的其他基金
Effector-Regulator Immune Interactions During Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病期间效应器-调节器免疫相互作用
- 批准号:1059550910595509
- 财政年份:2022
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Effector-Regulator Immune Interactions During Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病期间效应器-调节器免疫相互作用
- 批准号:1035999810359998
- 财政年份:2022
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ShEEP Request for Cytek Aurora Spectral Flow Cytometer
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- 财政年份:2019
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:93389889338988
- 财政年份:2017
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:1024884410248844
- 财政年份:2017
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:94835339483533
- 财政年份:2017
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:1044706110447061
- 财政年份:2017
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Immune Dysregulation During Multiple Sclerosis Relapse
多发性硬化症复发期间的免疫失调
- 批准号:99296709929670
- 财政年份:2016
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
Immune Dysregulation During Multiple Sclerosis Relapse
多发性硬化症复发期间的免疫失调
- 批准号:99158489915848
- 财政年份:2016
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
CNS-Specific Regulatory CD8+ T Cells in Autoimmune Demyelination
CNS 特异性调节 CD8 T 细胞在自身免疫性脱髓鞘中的作用
- 批准号:86489968648996
- 财政年份:2011
- 资助金额:$ 31.94万$ 31.94万
- 项目类别:
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