Intravascular Immune Surveillance by Anti-viral T Cells

抗病毒 T 细胞的血管内免疫监视

基本信息

  • 批准号:
    10304141
  • 负责人:
  • 金额:
    $ 63.66万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-11-17 至 2025-10-31
  • 项目状态:
    未结题

项目摘要

CD8 T cells mediate adaptive immune responses against malignant tumors and intracellular pathogens. In order to exert their protective effector functions, they must engage in physical contacts with their targets. Thus, T cells migrate actively within the body in search of cognate antigens. Following encounter of viral antigens, anti-viral T cells make a series of fate decisions that determine their differentiation into phenotypically diverse effector (Teff) and memory cell (Tmem) subsets that possess specialized properties. The rules that govern the magnitude, functional differentiation, migratory properties and life-span of virus-specific T cell subsets are incompletely understood. Recent work has shown that the chemokine receptor CX3CR1 identifies three distinct CD8+ Teff and Tmem subsets that are induced by systemic viral infections. The largest subset expresses high levels of CX3CR1 and is permanently devoid of lymph node homing receptors. Consequently, CX3CR1hi Teff and Tmem (referred to as effector memory cells, or Tem) are abundant in blood and spleen, but absent from other lymphoid tissues. Contrary to the prevailing paradigm, preliminary experiments indicate that CX3CR1hi Teff and Tem are also excluded from the extravascular compartment in non-lymphoid tissues. Instead, multi-photon intravital microscopy observations indicate that large numbers of CX3CR1hi T cells marginate and arrest within venules and then crawl against the blood stream across the capillary bed into arterioles where the CX3CR1hi T cells are found at high density. The present project will explore the hypothesis that crawling Teff and Tem employ unique molecular mechanisms to adhere and migrate within the microvasculature to survey microvascular endothelial cells for antigens and to receive signals that shape the Tmem repertoire. This hypothesis will be addressed in two specific aims: (1.) to characterize the migratory properties of intravascular anti-viral Teff and Tmem; and (2.) to assess the impact of intravascular T cell crawling on Teff and Tmem differentiation and function.
CD 8 T细胞介导针对恶性肿瘤的适应性免疫应答, 病原体为了发挥它们的保护效应器功能,它们必须参与物理活动, 与他们的目标接触。因此,T细胞在体内积极迁移以寻找同源物。 抗原在遇到病毒抗原后,抗病毒T细胞做出一系列命运决定 其决定了它们分化成表型多样性效应细胞(Teff)和记忆细胞 (THEORY)具有专门属性的子集。控制大小的规则, 病毒特异性T细胞亚群的功能分化、迁移特性和寿命, 不完全理解。最近的研究表明趋化因子受体CX 3CR 1 鉴定了由系统性病毒感染诱导的三种不同的CD 8 + Teff和Teff亚群。 最大的亚群表达高水平的CX 3CR 1,并且永久性地没有淋巴结转移。 归巢受体因此,CX 3CR 1hi Teff和Teff(称为效应记忆细胞, 或Tem)在血液和脾脏中丰富,但在其他淋巴组织中缺乏。违反 在流行的范例中,初步实验表明CX 3CR 1hi Teff和Tem也是 从非淋巴组织的血管外隔室中排除。相反,多光子 活体显微镜观察表明,大量CX 3CR 1hi T细胞边缘化, 并在小静脉内停滞,然后逆着血流爬行穿过毛细血管床, 小动脉中发现高密度的CX 3CR 1hi T细胞。本项目将探讨 爬行Teff和Tem采用独特的分子机制粘附和 在微血管系统内迁移以检测微血管内皮细胞的抗原, 接收信号来塑造Tendon的所有功能。这一假设将在两个具体的 目的:(1.)表征血管内抗病毒Teff和Teff的迁移性质;和 (2.)评估血管内T细胞爬行对Teff和Teff分化的影响, 功能

项目成果

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ULRICH H VON ANDRIAN其他文献

ULRICH H VON ANDRIAN的其他文献

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{{ truncateString('ULRICH H VON ANDRIAN', 18)}}的其他基金

Neutrophil Dynamics in Nasal Mucosa
鼻粘膜中性粒细胞动态
  • 批准号:
    10638705
  • 财政年份:
    2023
  • 资助金额:
    $ 63.66万
  • 项目类别:
Intravascular Immune Surveillance by Anti-viral T Cells
抗病毒 T 细胞的血管内免疫监视
  • 批准号:
    10509385
  • 财政年份:
    2020
  • 资助金额:
    $ 63.66万
  • 项目类别:
Regulation of Skin Inflammation by Nociceptive Sensory Neurons
伤害性感觉神经元对皮肤炎症的调节
  • 批准号:
    9268505
  • 财政年份:
    2015
  • 资助金额:
    $ 63.66万
  • 项目类别:
Mechanisms and Immunological Consequences of Host-Virus Interactions
宿主-病毒相互作用的机制和免疫学后果
  • 批准号:
    9110861
  • 财政年份:
    2014
  • 资助金额:
    $ 63.66万
  • 项目类别:
Mechanisms and Immunological Consequences of Host-Virus Interactions
宿主-病毒相互作用的机制和免疫学后果
  • 批准号:
    9322437
  • 财政年份:
    2014
  • 资助金额:
    $ 63.66万
  • 项目类别:
Mechanisms and Immunological Consequences of Host-Virus Interactions
宿主-病毒相互作用的机制和免疫学后果
  • 批准号:
    8742510
  • 财政年份:
    2014
  • 资助金额:
    $ 63.66万
  • 项目类别:
Generation and Function of NK Cell Memory
NK细胞记忆的产生和功能
  • 批准号:
    8701645
  • 财政年份:
    2013
  • 资助金额:
    $ 63.66万
  • 项目类别:
Generation and Function of NK Cell Memory
NK细胞记忆的产生和功能
  • 批准号:
    8881098
  • 财政年份:
    2013
  • 资助金额:
    $ 63.66万
  • 项目类别:
Generation and Function of NK Cell Memory
NK细胞记忆的产生和功能
  • 批准号:
    8719937
  • 财政年份:
    2013
  • 资助金额:
    $ 63.66万
  • 项目类别:
Generation and Function of NK Cell Memory
NK细胞记忆的产生和功能
  • 批准号:
    9319128
  • 财政年份:
    2013
  • 资助金额:
    $ 63.66万
  • 项目类别:

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