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

免疫系统是用来保护我们免受外来病原体如细菌和病毒的侵害的。然而，该系统并不完美，有时会攻击个体自身组织（称为自身免疫）。自身免疫在人群中并不罕见，包括糖尿病、类风湿关节炎和恶性贫血等疾病。为了研究与免疫系统为何以及如何启动宿主相关的细节，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这是一种器官特异性的胃部自身免疫性疾病。患有自身免疫性胃炎的人会产生一种特异性的自身免疫反应，直接针对胃的分泌酸的细胞——壁细胞。壁细胞还产生一种叫做内在因子的物质，它是吸收饮食中的维生素B12所必需的。维生素B12摄取不足导致红细胞形成异常和贫血；因此有了恶性贫血这个词。与免疫系统相关的一个悬而未决的问题是，是什么调节了整个系统，使其不会在每个人身上引发自身免疫。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完成的。关于这些细胞的许多重要问题仍未得到解答。例如，我们不知道这些细胞是如何产生的，也不知道它们是如何阻止自身反应性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，我们正在解决一些围绕诱导和保护我们免受自身免疫的事件的问题。通过使用循环中大多数淋巴细胞具有相同特异性的小鼠（tcr转基因），我们可以跟踪这些细胞的命运，寻找具有不同特征的细胞；比如抑制免疫反应的能力。

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.