Myeloid‐derived suppressor cells mediate tolerance induction in autoimmune disease

Summary In multiple sclerosis ( MS ) T cells aberrantly recognize self‐peptides of the myelin sheath and attack the central nervous system ( CNS ). Antigen‐specific peptide immunotherapy, which aims to restore tolerance while avoiding the use of non‐specific immunosuppressive drugs, is a promising approach to combat autoimmune disease, but the cellular mechanisms behind successful therapy remain poorly understood. Myeloid‐derived suppressor cells ( MDSC s) have been studied intensively in the field of cancer and to a lesser extent in autoimmunity. Because of their suppressive effect on the immune system in cancer, we hypothesized that the development of MDSC s and their interaction with CD 4 + T cells could be beneficial for antigen‐specific immunotherapy. Hence, changes in the quantity, phenotype and function of MDSC s during tolerance induction in our model of MS were evaluated. We reveal, for the first time, an involvement of a subset of MDSC s, known as polymorphonuclear ( PMN )‐ MDSC s, in the process of tolerance induction. PMN ‐ MDSC s were shown to adopt a more suppressive phenotype during peptide immunotherapy and inhibit CD 4 + T‐cell proliferation in a cell‐contact‐dependent manner, mediated by arginase‐1. Moreover, increased numbers of tolerogenic PMN ‐ MDSC s, such as observed over the course of peptide immunotherapy, were demonstrated to provide protection from disease in a model of experimental autoimmune encephalomyelitis.