Pivotal role of VLA-1 in CD8 T cell retention & survival
Pivotal role of VLA-1 in CD8 T cell retention & survival
批准号:
6598415
负责人:
DAVID James TOPHAM
金额:
$34.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-05-01 至 2008-04-30
关键词:
anamnestic reaction apoptosis cell aggregation cell cell interaction cell migration collagen cytotoxic T lymphocyte flow cytometry gene targeting genetically modified animals immunocytochemistry immunologic memory influenza integrins laboratory mouse leukocyte activation /transformation lung microorganism immunology protein binding protein protein interaction protein structure function receptor expression secondary infection terminal nick end labeling transfection /expression vector virus cytopathogenic effect
中文摘要
描述(由申请人提供):病毒特异性T细胞记忆对于保护宿主免受相同或相关病毒的二次暴露很重要。这些记忆T细胞的定位及其激活状态决定了二次免疫反应的效率。大量淋巴外记忆细胞在功能上不同于淋巴记忆细胞。这些记忆T细胞在非淋巴组织中保留的机制尚不清楚。我们提供的初步数据显示,病毒特异性CD8+ T细胞在流感感染期间迅速获得整合素VLA-1的表达。VLA-1是I型和IV型胶原蛋白的受体。在感染消退期间,vra -1+流感特异性CD8 T细胞表现出对凋亡的抵抗力,并选择性地在肺和其他非淋巴组织中积累。免疫后抑制vra -1+可减少肺部流感特异性T细胞的数量,损害继发免疫。由此,我们形成了一种假设,即VLA-1+ CD8 T细胞与I型和IV型胶原结合可促进记忆T细胞在非淋巴组织内的保留和存活。这些CD8+/VLA - 1+ CD8 T细胞可能优先保留在非淋巴组织中,为抵抗继发性感染提供第一道防线。本实验将通过胶原结合来确定vas -1在组织中病毒特异性CD8 T细胞的保留和存活中的作用。我们还将测试预测,即vra -1+记忆T细胞在功能上是独特的,对二次免疫保护很重要。
英文摘要
DESCRIPTION (provided by applicant): Virus-specific T cell memory is important to protect the host from secondary exposure to the same or related viruses. The localization of these memory T cells and their activation status determines the efficiency of the secondary immune response. A substantial extralymphoid memory population that is functionally distinct from the lymphoid memory cells has recently been described. The mechanism by which these memory T cells can be retained in non-lymphoid tissue is not known. We present preliminary data that show virus specific CD8+ T cells rapidly acquire expression of the integrin VLA-1 during influenza infection. VLA-1 is the receptor for Type I and IV collagen. VLA-1+ flu-specific CD8 T cells show resistance to apoptosis and selectively accumulate in the lung and other non-lymphoid tissues during resolution of the infection. Postimmune inhibition of VLA-1+ reduces the number of flu-specific T cells in the lung and compromises secondary immunity. From this we have formed the hypothesis that binding of VLA-1+ CD8 T cells to Types I and IV collagen promotes retention and survival of memory T cells within non-lymphoid tissues. These CD8+/VLA - 1+ CD8 T cells may be preferentially retained in non-lymphoid tissues to provide a first line of defense against secondary infection. The experiments in this proposal will establish the role of VLA-1 in the retention and survival of virus-specific CD8 T cells in tissue via collagen-binding. We will also test the prediction that the VLA-1+ memory T cells are functionally distinct and important for secondary immune protection.
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Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection
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批准号:10241370
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项目类别:
-
资助金额:$40.8万
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财政年份:2014
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负责人:DAVID James TOPHAM
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依托单位:
Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection
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批准号:10689185
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项目类别:
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资助金额:$41.88万
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财政年份:2014
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负责人:DAVID James TOPHAM
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依托单位:
Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection
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批准号:10002196
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项目类别:
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资助金额:$40.79万
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财政年份:2014
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负责人:DAVID James TOPHAM
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依托单位:
Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection
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批准号:10477328
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项目类别:
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资助金额:$40.81万
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财政年份:2014
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负责人:DAVID James TOPHAM
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依托单位:
Pivotal role of VLA-1 in CD8 T cell retention & survival
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批准号:7072800
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项目类别:
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资助金额:$30.76万
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财政年份:2003
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负责人:DAVID James TOPHAM
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依托单位:
Pivotal role of VLA-1 in CD8 T cell retention & survival
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批准号:6895566
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项目类别:
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资助金额:$31.5万
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财政年份:2003
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负责人:DAVID James TOPHAM
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依托单位:
Pivotal role of VLA-1 in CD8 T cell retention & survival
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批准号:6740190
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项目类别:
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资助金额:$31.5万
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财政年份:2003
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负责人:DAVID James TOPHAM
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依托单位:
Pivotal role of VLA-1 in CD8 T cell retention & survival
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批准号:7227061
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项目类别:
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资助金额:$29.87万
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财政年份:2003
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负责人:DAVID James TOPHAM
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依托单位:
Dynamics of CD8 T cell migration in the influenza-infected airways ....
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批准号:8692179
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项目类别:
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资助金额:$34.29万
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财政年份:--
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负责人:DAVID James TOPHAM
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依托单位:
Dynamics of CD8 T cell migration in the influenza-infected airways ....
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批准号:8850801
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项目类别:
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资助金额:$38.04万
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财政年份:--
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负责人:DAVID James TOPHAM
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依托单位:
Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection
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批准号:9791603
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项目类别:
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资助金额:$40.79万
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财政年份:--
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负责人:DAVID James TOPHAM
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依托单位:
Dynamics of CD8 T cell migration in the influenza-infected airways ....
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批准号:9065654
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项目类别:
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资助金额:$38.05万
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财政年份:--
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负责人:DAVID James TOPHAM
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依托单位:
Dynamics of CD8 T cell migration in the influenza-infected airways ....
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批准号:9284407
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项目类别:
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资助金额:$38.05万
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财政年份:--
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负责人:DAVID James TOPHAM
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依托单位:
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