Journal article
CD8+ T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease
PloS one, Vol.8(6), pp.e66772-e66772
06/21/2013
DOI: 10.1371/journal.pone.0066772
PMCID: PMC3689655
PMID: 23805274
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.
Details
- Title: Subtitle
- CD8+ T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease
- Creators
- Andrew F TylerJason P MendozaMihail FiranNitin J Karandikar
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(6), pp.e66772-e66772
- DOI
- 10.1371/journal.pone.0066772
- PMID
- 23805274
- PMCID
- PMC3689655
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- Drug-Induced Regulatory CD8+ T Cells
- Language
- English
- Date published
- 06/21/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047608302771
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