Notch signalling in peripheral T cell differentiation and regulatory T cell development

摘要

The immune system has evolved to being an incredibly adaptive and effective defence against pathogenic microorganisms and cancer. However, to protect the organism, it is equally important to maintain im-munologic tolerance to harmless substances, e.g. food components and constituents of the own body. Lack of immunologic tolerance may lead to allergies or autoimmune diseases, such as multiple sclerosis, diabetes and rheumatoid arthritis. The immune response therefore has to be tightly regulated. Autoreactive immune cells are eliminated very efficiently early in their development by complex selection processes. For T helper cells (T_H), which are the key players in the complex network of the adaptive immune system, this process takes place in the thymus. The suppressive activity of a subset of T_H cells, the regulatory T cells, was recently recognized as the second major mechanism underlying induction and maintenance of tolerance. Regulatory T cells suppress an uncontrolled and inappropriate activation of immune cells in the periphery of the body. The population of regulatory T cells is merely defined on the basis of their suppressive activity and shows a high degree of heterogeneity with respect to the expression of surface markers as well as effector molecules. It is therefore not yet clear whether regulatory T cells mostly arise in the thymus or later upon contact with the antigen in the periphery. Generally, however, these cells are believed to represent a separate differentiation state of T_H cells.