CD8.sup.+ T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease

The exact mechanism of glatiramer acetate (GA, Copaxone®), an FDA-approved immunomodulatory therapy for multiple sclerosis (MS), remains unclear after decades of research. Previously, we have shown that GA therapy of MS induces CD8.sup.+ T cell responses that can potentially suppress pathogenic CD4.sup.+ T cell responses. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we now demonstrate that CD8.sup.+ T cells are necessary in mediating the therapeutic effects of GA. Further, adoptive transfer of GA-induced CD8.sup.+ T cells resulted in amelioration of EAE, establishing a role as a viable immunotherapy in demyelinating disease. Generation of these cells required indoleamine-2,3-dioxygenase (IDO), while suppressive function depended on non-classical MHC class I, IFN-[gamma], and perforin expression. GA-induced regulatory myeloid cells, previously shown to activate CD4.sup.+ regulatory T cells in an antigen-independent manner, required CD8.sup.+ T cells for disease suppression in vivo. These studies demonstrate an essential role for CD8.sup.+ T cells in GA therapy and identify their potential as an adoptive immunotherapeutic agent.