title: Regulatory T cell-based immunotherapies in experimental autoimmune myasthenia gravis.
abstract: 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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. miriso@openu.ac.il
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Souroujon
authors.forename: Revital
authors.initials: R
authors.lastname: Aricha
authors.forename: Tali
authors.initials: T
authors.lastname: Feferman
authors.forename: Keren
authors.initials: K
authors.lastname: Mizrachi
authors.forename: Debby
authors.initials: D
authors.lastname: Reuveni
authors.forename: Sara
authors.initials: S
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D015850:Interleukin-6 / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000637:transplantation; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D015850:Interleukin-6