The Relationship between TCR Revision and Follicular Helper T Cells
TCR 修正与滤泡辅助 T 细胞的关系
基本信息
- 批准号:8423326
- 负责人:
- 金额:$ 22.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-03-01 至 2014-08-28
- 项目状态:已结题
- 来源:
- 关键词:Adoptive TransferAffinityAntigen ReceptorsAutoantigensAutoimmunityB-LymphocytesBLR1 geneBacterial InfectionsBone MarrowCD 200CD28 geneCD4 Positive T LymphocytesCD4/CD8 ratio procedureCell CommunicationCell surfaceCellsCharacteristicsChimera organismChronicCommunicationComplexDancingDendritic CellsEndogenous RetrovirusesErythrocytesFrequenciesGenesGenetic RecombinationGenetic TranscriptionGoalsGrantHelper-Inducer T-LymphocyteImmune responseImmunoglobulin Class SwitchingImmunologyInterleukin-10Interleukin-17Interleukin-4LymphocyteMediatingMesenteryModelingMouse Mammary Tumor VirusMusPathway interactionsPatternPeripheralPhenotypePopulationProcessProteinsRelative (related person)ReporterRiskSTAT3 geneSelf ToleranceSheepSignal TransductionSignaling MoleculeSpleenStructure of aggregated lymphoid follicle of small intestineStructure of germinal center of lymph nodeSuperantigensSurfaceSurface AntigensT-Cell ReceptorT-LymphocyteTNFRSF5 geneTNFSF5 geneTestingTransgenic MiceTransgenic OrganismsUrsidae FamilyWorkage relatedarmcell typecytokinelymph nodesmammary tumor virusmigrationpreventprogramsrecombinaseresearch studytranscription factor
项目摘要
DESCRIPTION (provided by applicant): Self-tolerance of mature, peripheral CD4+ T cells in Vb5 transgenic (Tg) mice occurs through two pathways, deletion and T cell receptor (TCR) revision. Both processes are driven by chronic encounter with a peripherally expressed self-antigen encoded by mouse mammary tumor virus (Mtv) 8. Recognition of Mtv-8 expressed by dendritic cells renders CD4+Vb5+ T cells anergic and results in their deletion and the concomitant inversion of the peripheral CD4:CD8 ratio. T cells that chronically recognize Mtv-8 on B cells instead enter the germinal center and undergo TCR revision. During the process of TCR revision, T cells lose Vb5 surface expression, upregulate expression of the lymphocyte-specific recombinase machinery (RAG1, RAG2, and TdT), and rearrange endogenous TCR Vb genes. Deletion of Rag in peripheral T cells blocks TCR revision. Post revision T cells are Vb5- and fail to recognize Mtv-8, yet express a diverse TCRb repertoire and are self-MHC restricted and functional. The goal of this exploratory grant is to place the population of revising T cells in the context of a defined T cell subpopulation of known function. Our previous characterization of T cells in the process of TCR revision hint at a phenotypic overlap with the follicular helper T cell compartment. With this pilot grant, we will determine the relationship between the frequencies of revising T cells and germinal center B and T cells, and determine whether revising T cells bear the phenotypic and functional characteristics of follicular helper T cells. These experiments will help place TCR revision within the larger framework of T cell immunology, and will explore how TCR revision may impact the B cell arm of the adaptive immune response.
描述(由申请方提供):Vb 5转基因(Tg)小鼠中成熟外周CD 4 + T细胞的自身耐受通过两种途径发生,即缺失和T细胞受体(TCR)修正。这两个过程都是由小鼠乳腺肿瘤病毒(Mtv)8编码的外周表达的自身抗原的慢性遭遇驱动的。树突状细胞表达的Mtv-8的识别使CD 4 + Vb 5 + T细胞无反应性,并导致其缺失和伴随的外周CD 4:CD 8比率的倒置。长期识别B细胞上Mtv-8的T细胞进入生殖中心并进行TCR修正。在TCR修复过程中,T细胞失去Vb 5表面表达,上调淋巴细胞特异性重组酶机制(RAG 1、RAG 2和TdT)的表达,并重排内源性TCR Vb基因。外周T细胞中Rag的缺失阻断TCR修正。修正后的T细胞是Vb 5-,不能识别Mtv-8,但表达不同的TCRb库,是自身MHC限制性和功能性的。这项探索性资助的目标是将修订的T细胞群体置于已知功能的定义的T细胞亚群的背景下。我们先前对TCR修订过程中T细胞的表征暗示了与滤泡辅助T细胞区室的表型重叠。利用该试点基金,我们将确定修正T细胞与生发中心B和T细胞的频率之间的关系,并确定修正T细胞是否具有滤泡辅助T细胞的表型和功能特征。这些实验将有助于将TCR修订置于T细胞免疫学的更大框架内,并将探索TCR修订如何影响适应性免疫应答的B细胞臂。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Pamela J Fink其他文献
Pamela J Fink的其他文献
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{{ truncateString('Pamela J Fink', 18)}}的其他基金
Basic Training at the Intersection of Innate and Adaptive Immunity in Disease
疾病中先天免疫和适应性免疫交叉点的基础训练
- 批准号:
8713922 - 财政年份:2013
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$ 22.51万 - 项目类别:
Basic Training at the Intersection of Innate and Adaptive Immunity in Disease
疾病中先天免疫和适应性免疫交叉点的基础训练
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9273432 - 财政年份:2013
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Basic Training at the Intersection of Innate and Adaptive Immunity in Disease
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- 批准号:
8548071 - 财政年份:2013
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$ 22.51万 - 项目类别:
The Relationship between TCR Revision and Follicular Helper T Cells
TCR 修正与滤泡辅助 T 细胞的关系
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8231750 - 财政年份:2012
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