Pivotal role of VLA-1 in CD8 T cell retention & survival

VLA-1 在 CD8 T 细胞保留中的关键作用

• 批准号: 7072800
• 负责人: DAVID James TOPHAM
• 金额: $ 30.76万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072800
• 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

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.

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非​​常重要。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。最近描述了一个在功能上不同于淋巴记忆细胞的大量淋巴外记忆细胞群。这些记忆 T 细胞保留在非淋巴组织中的机制尚不清楚。我们提供的初步数据表明，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。 VLA-1+流感特异性CD8 T细胞表现出对细胞凋亡的抵抗力，并在感染消退期间选择性地积聚在肺和其他非淋巴组织中。 VLA-1+ 的免疫后抑制会减少肺部流感特异性 T 细胞的数量，并损害二次免疫。由此我们形成了这样的假设：VLA-1+ CD8 T 细胞与 I 型和 IV 型胶原蛋白的结合可促进非淋巴组织内记忆 T 细胞的保留和存活。这些 CD8+/VLA-1+ CD8 T 细胞可能会优先保留在非淋巴组织中，以提供针对继发感染的第一道防线。本提案中的实验将确定 VLA-1 通过胶原蛋白结合在组织中病毒特异性 CD8 T 细胞保留和存活中的作用。我们还将测试 VLA-1+ 记忆 T 细胞功能独特且对于二级免疫保护很重要的预测。