We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
CD8<sup>+</sup> T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease.
- Authors
Tyler, Andrew F.; Mendoza, Jason P.; Firan, Mihail; Karandikar, Nitin J.
- Abstract
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+ T cell responses that can potentially suppress pathogenic CD4+ T cell responses. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we now demonstrate that CD8+ T cells are necessary in mediating the therapeutic effects of GA. Further, adoptive transfer of GA-induced CD8+ 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-γ, and perforin expression. GA-induced regulatory myeloid cells, previously shown to activate CD4+ regulatory T cells in an antigen-independent manner, required CD8+ T cells for disease suppression in vivo. These studies demonstrate an essential role for CD8+ T cells in GA therapy and identify their potential as an adoptive immunotherapeutic agent.
- Subjects
CD8 antigen; T cells; GLATIRAMER acetate; DEMYELINATION; AUTOIMMUNE diseases; IMMUNOREGULATION; IMMUNOLOGY; ANIMAL models in research
- Publication
PLoS ONE, 2013, Vol 8, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0066772