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

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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.