Effector and memory CD8+ T cell responses to engineered influenza A escape mutants

效应和记忆 CD8 T 细胞对工程甲型流感逃逸突变体的反应

• 批准号: nhmrc : 454312
• 负责人: Prof Katherine Kedzierska
• 金额: $ 31.02万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/effector-memory-cd8-escape-mutants/97329
• 关键词: Effector; memory; CD8+; cell; responses

T cells are a critical component of the immune system after infection with viruses. In particular, virus-specific CD8+ T cells can clear viral infections by killing virally-infected cells and the release of immunomodulators. These are called effector T cells. After the viral infection is cleared, a small proportion of T cells (around 5 to 10%) survives for many years and constitute a memory pool of virus-specific T cells. Memory T cells provide a rapid and effective protection in case of a repeated infection with the same virus, and hence result in a less severe disease. However, viruses often mutate their genes to escape such efficient T cell responses. In this study, we will investigate T cell responses after infection with mutated strains of influenza viruses. We will engineer a panel of mutant influenza viruses, which alter the nature and characteristics of T cells. We will analyse how efficient are these T cells and whether they can protect against a normal strain of influenza A. Subsequently, we will characterise quantitative and qualitative aspects of memory T cell pools after infection with mutant influenza viruses. Since a number of viruses such as influenza, HIV and HCV rapidly mutate their genes, our study will not only address the question of T cell responses to mutated influenza viruses, but also will provide an excellent model for investigating protective T cell responses to other viral infections.

T细胞是感染病毒后免疫系统的重要组成部分。特别是，病毒特异性CD8+ T细胞可以通过杀死病毒感染的细胞和释放免疫调节剂来清除病毒感染。这些被称为效应T细胞。在病毒感染被清除后，一小部分T细胞（约5 - 10%）存活多年，构成了病毒特异性T细胞的记忆库。记忆T细胞在同一病毒反复感染的情况下提供快速有效的保护，因此导致较轻的疾病。然而，病毒经常通过基因突变来逃避这种有效的T细胞反应。在这项研究中，我们将研究突变流感病毒株感染后的T细胞反应。我们将设计一组突变流感病毒，改变T细胞的性质和特征。我们将分析这些T细胞的效率，以及它们是否能抵御正常的甲型流感病毒株。随后，我们将描述突变流感病毒感染后记忆T细胞池的定量和定性方面。由于流感、HIV和HCV等病毒的基因迅速突变，我们的研究不仅将解决T细胞对突变流感病毒的反应问题，而且将为研究保护性T细胞对其他病毒感染的反应提供一个很好的模型。