CD8(+) 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(+) T cell responses that can potentially suppress pathogenic CD4(+)...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3689655?pdf=render |
| _version_ | 1819163343636660224 |
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| author | Andrew F Tyler Jason P Mendoza Mihail Firan Nitin J Karandikar |
| author_facet | Andrew F Tyler Jason P Mendoza Mihail Firan Nitin J Karandikar |
| author_sort | Andrew F Tyler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T17:42:38Z |
| format | Article |
| id | doaj.art-a1fe190c1f2e47a78d5f41c1aadaf85e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T17:42:38Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a1fe190c1f2e47a78d5f41c1aadaf85e2022-12-21T18:18:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6677210.1371/journal.pone.0066772CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease.Andrew F TylerJason P MendozaMihail FiranNitin J KarandikarThe 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.http://europepmc.org/articles/PMC3689655?pdf=render |
| spellingShingle | Andrew F Tyler Jason P Mendoza Mihail Firan Nitin J Karandikar CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. PLoS ONE |
| title | CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. |
| title_full | CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. |
| title_fullStr | CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. |
| title_full_unstemmed | CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. |
| title_short | CD8(+) T Cells Are Required For Glatiramer Acetate Therapy in Autoimmune Demyelinating Disease. |
| title_sort | cd8 t cells are required for glatiramer acetate therapy in autoimmune demyelinating disease |
| url | http://europepmc.org/articles/PMC3689655?pdf=render |
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