Functional Properties of Cytotoxic T Cells that Suppress HIV: The Good And The Bad

抑制 HIV 的细胞毒性 T 细胞的功能特性：好与坏

• 批准号: G0701335/1
• 负责人: Julie Glanville
• 金额: $ 28.31万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701335%2F1
• 关键词: Functional; Properties; Cytotoxic; Cells; Suppress

An individual with Human Immunodeficiency Virus (HIV) attacks the infection with specialised white blood cells called cytotoxic T lymphocytes (CTL). Despite making large numbers of CTL, HIV infection cannot be cured or even prevented from progressing to AIDS. However, some individuals remain well for ten years after infection, and others succumb after a few months. We propose that this variable progression time between individuals is because some cytotoxic T cells are more effective at suppressing virus than others. Defining the characterisitcs of exactly what makes a CTL effective is very important to design an HIV vaccine that works. We aim to do this by studying CTL from volunteers with HIV, immortalised into clones. We will then compare how effectively each CTL clone suppresses HIV replication in infected cells in the laboratory. By identifying the most effective CTL clones and comparing them with less effective CTL clones, we can define those characteristics associated with good HIV suppression. One method we will use analyses the expression of thousands of genes simultaneously. This may identify a unique fingerprint for Good CTL, that can open new areas of research into the proteins that Good CTL express and may even identify new anti-viral factors, or drug targets.

人类免疫缺陷病毒（HIV）感染者用称为细胞毒性T淋巴细胞（CTL）的特殊白色血细胞攻击感染。尽管产生了大量的CTL，但HIV感染无法治愈，甚至无法阻止其发展为AIDS。然而，有些人在感染后十年内仍然很好，而其他人在几个月后死亡。我们认为，个体之间这种可变的进展时间是因为一些细胞毒性T细胞比其他细胞更有效地抑制病毒。明确CTL的有效特性对于设计有效的HIV疫苗非常重要。我们的目标是通过研究来自艾滋病志愿者的CTL来实现这一目标，这些CTL被永生化为克隆。然后，我们将在实验室中比较每个CTL克隆如何有效地抑制感染细胞中的HIV复制。通过鉴定最有效的CTL克隆并将它们与不太有效的CTL克隆进行比较，我们可以确定与良好的HIV抑制相关的那些特征。我们将使用的一种方法是同时分析数千个基因的表达。这可能会识别出Good CTL的独特指纹，这可以为Good CTL表达的蛋白质开辟新的研究领域，甚至可能识别新的抗病毒因子或药物靶点。