Mechanisms of action of regulatory lymphocytes and a possibility to use them in the treatment of autoimmune diseases and GvH reactions.

Basic characteristic of the immune system is its ability to distinguish self-molecules, cells, tissues and organs from not self, to tolerate self and dispose of not self. Immunosuppressive mechanisms, especially those mediated by regulatory lymphocytes, play a paramount role in the tolerance mechanisms. When there is an abnormal quantity and/or quality of regulatory cells, various autoimmune diseases are induced, e.g. SLE, RA, T1D, IBD, MS, and others.In recent years, a great progress was achieved in the field how to profit from immunosuppressive properties of T regulatory cells (Treg) in the treatment of patients suffering from autoimmune disorders or transplantation rejections. Nowadays, there are possibilities to up-regulate the function of patient's Tregs or supplement their low numbers. We can up-regulate the function of Treg cells in an affected organism by treatment by low dosage of IL-2 or to treat patients by in vitro expanded Treg cells themselves. Induced Tregs are, however, polyspecific, therefore they have been preferentially used for the treatment graft versus host reactions and some autoimmune disorders only. For those autoimmune diseases, where specific autoantigens are known, Treg cells equipped by antigen-specific chimeric T cell receptor (CARs) were introduced for their treatment (Tab. 1, Fig. 2, Ref. 47). Keywords: AIRE, autoimmune diseases, CAR, cytokines, iNKT cells, regulatory B and T cells.