Regulatory T cell-based immunotherapies in experimental autoimmune myasthenia gravis

Establishment of tolerance in myasthenia gravis (MG) involves regulatory T (T_reg) cells. Experimental autoimmune MG (EAMG) in rats is a suitable model for assessing the contribution of T_reg cells to the immunopathology of the disease and for testing novel T_reg cell-based treatment modalities. We have studied two immunotherapeutic approaches for targeting of T_reg cells in myasthenia. By one approach we demonstrated that treatment of sick rats by ex vivo-generated exogenous T_reg cells derived from healthy donors suppressed EAMG. By a different approach, we aimed at affecting the endogenous T_reg/Th17 cell balance by targeting IL-6, which has a key role in controlling the equilibrium between pathogenic Th17 and suppressive T_reg cells. We found that treatment of myasthenic rats by neutralizing anti-IL-6 antibodies shifted this equilibrium in favor of T_reg cells and led to suppression of EAMG. Our results show that T_reg cells could serve as potential targets in treating MG patients.