CD4 T cell-mediated tolerance and autoimmunity to the gastric H/K ATPase in genetically manipulated mice

CD4 T 细胞介导的基因操作小鼠对胃 H/K ATP 酶的耐受性和自身免疫

• 批准号: nhmrc : 124309
• 负责人: Prof Ban-Hock Toh
• 金额: $ 19.72万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/cd4-t-cell-manipulated-mice/100066
• 关键词: CD4; cell; mediated; tolerance; autoimmunity

The immune system is designed to protect us from foreign pathogens such as bacteria and viruses. However, the system is not prefect and sometimes attacks an individual's own tissue (termed autoimmunity). Autoimmunity is not uncommon in the population, including diseases such as diabetes, rheumatoid arthritis and pernicious anaemia, to name a few. To study the details associated with why and how the immune system can turn on the host, we use animal models which mimic the human diseases. The model we use is a mouse model for autoimmune gastritis which is an organ-specific autoimmune disorder of the stomach. People with autoimmune gastritis produce a specific autoimmune response directed at the acid secreting cells of the stomach call parietal cells. Parietal cells also produced a substance called intrinsic factor which is needed for the absorption of vitamin B12 from the diet. The lack of vitamin B12 uptake results in abnormal red blood cell formation and anaemia; hence the term pernicious anaemia. One of the unanswered questions associated with the immune system is what regulates the whole system so that it does not induce autoimmunity in everyone. The mechanisms which control or prevent autoimmunity is the subject of much debate. There is good evidence that regulation of the immune system is performed by specific suppression by regulatory cells. Many important question about these cells remain unanswered. For example, it is not known how these cells are generated or how they prevent the autoreactive cells from performing their harmful behaviour. Using our animal model for autoimmune gastritis, we are addressing some of the questions which surround the events which induce and protect us from autoimmunity. By using mice in which most of the lymphocytes in the circulation are of the same specificity (TCR-transgenic), we can follow the fate of those cells and look for cells with different characteristics; such as the ability to supress an immune response.

免疫系统旨在保护我们免受细菌和病毒等外来病原体的侵害。然而，该系统并不完美，有时会攻击个体自身的组织（称为自身免疫）。自身免疫在人群中并不少见，包括糖尿病、类风湿性关节炎和恶性贫血等疾病。为了研究免疫系统为什么以及如何启动宿主的细节，我们使用了模拟人类疾病的动物模型。我们使用的模型是自身免疫性胃炎的小鼠模型，其是胃的器官特异性自身免疫性疾病。患有自身免疫性胃炎的人产生针对胃的酸分泌细胞（称为壁细胞）的特定自身免疫反应。壁细胞还产生一种称为内在因子的物质，这种物质是从饮食中吸收维生素B12所必需的。缺乏维生素B12的吸收导致异常的红细胞形成和贫血;因此术语恶性贫血。与免疫系统相关的一个未回答的问题是，是什么调节了整个系统，使其不会在每个人身上诱导自身免疫。控制或预防自身免疫的机制是许多争论的主题。有充分的证据表明，免疫系统的调节是通过调节细胞的特异性抑制来进行的。关于这些细胞的许多重要问题仍然没有答案。例如，目前还不知道这些细胞是如何产生的，也不知道它们是如何防止自身反应细胞进行有害行为的。利用我们的自身免疫性胃炎动物模型，我们正在解决一些问题，这些问题围绕着诱导和保护我们免受自身免疫的事件。通过使用循环中大多数淋巴细胞具有相同特异性（TCR转基因）的小鼠，我们可以跟踪这些细胞的命运并寻找具有不同特征的细胞;例如抑制免疫反应的能力。