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: Miriam C Souroujon, Revital Aricha, Tali Feferman, Keren Mizrachi, Debby Reuveni, Sara Fuchs
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1274 Pg. 120-6 (Dec 2012) ISSN: 1749-6632 [Electronic] United States
• PMID: 23252906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 New York Academy of Sciences.

Chemical References

• Antibodies, Neutralizing
• Interleukin-6

Topics

• Animals
• Antibodies, Neutralizing (therapeutic use)
• Humans
• Immune Tolerance
• Immunotherapy (methods)
• Interleukin-6 (immunology)
• Myasthenia Gravis, Autoimmune, Experimental (immunology, therapy)
• Rats
• T-Lymphocytes, Regulatory (metabolism, transplantation)
• Th1 Cells (metabolism)
• Th17 Cells (metabolism)