T cells can protect our body very specifically against pathogens. However, sometimes these cells turn against our own body. This is referred to as autoimmunity. This is usually prevented by a special type of T cells, known as regulatory T cells. These cells have the ability to suppress the immune system. Due to this property, regulatory T cells can be used to inhibit unwanted immune responses in patients, such as those with autoimmune diseases or patients who have received an organ transplant. To do this, regulatory T cells are first isolated from a patient's blood, expanded in culture in the laboratory, and then reintroduced to the patient. There are different types of regulatory T cells. Some of them can change into regular T cells, which then no longer suppress the immune response. In fact, such cells could attack the body and thus worsen the disease. Therefore, it is very important to distinguish between stable and unstable regulatory T cells in order to be able to make safe regulatory T cell products. Until now, this has not been possible. In this project, we describe how we found a protein, called GPA33, that is very specifically present on stable regulatory T cells and not on unstable ones. We have shown that cells expressing GPA33 on their surface are generated in the thymus. This is important information, because we know from experiments in mice that stable regulatory T cells come from the thymus. Furthermore, regulatory T cells with GPA33 on their surface can be cultured well in the laboratory while maintaining their regulatory properties. We believe these cells are ideal for use in new therapies. For that reason, we have developed a method (which we have patented) that allows us to obtain these cells in a pure form. Finally, in this project, we discovered a new type of regulatory T cells. These cells possess so-called stem cell properties: they can multiply and produce both copies of themselves and other types of regulatory T cells. The properties of these stem cell-like regulatory T cells are essential for therapeutic regulatory T cells. Findings from this project are now being used to develop therapeutic products with regulatory T cells.