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

Andrew F. Tyler, Jason P. Mendoza, Mihail Firan, Nitin J. Karandikar

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere66772
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 21 2013

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T-cells
autoimmune diseases
Demyelinating Diseases
Autoimmune Diseases
T-lymphocytes
acetates
T-Lymphocytes
therapeutics
sclerosis
Multiple Sclerosis
Autoimmune Experimental Encephalomyelitis
encephalitis
Therapeutics
Indoleamine-Pyrrole 2,3,-Dioxygenase
Perforin
Immunomodulation
Adoptive Transfer
Therapeutic Uses
Regulatory T-Lymphocytes
Myeloid Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

CD8+ T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. / Tyler, Andrew F.; Mendoza, Jason P.; Firan, Mihail; Karandikar, Nitin J.

In: PLoS One, Vol. 8, No. 6, e66772, 21.06.2013.

Research output: Contribution to journalArticle

Tyler, Andrew F. ; Mendoza, Jason P. ; Firan, Mihail ; Karandikar, Nitin J. / CD8+ T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. In: PLoS One. 2013 ; Vol. 8, No. 6.
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