Role of T cells in inflammation caused by adenovirus vectors in the brain.
In many organs, E1-deleted human adenovirus vectors trigger antiviral T cell responses which limit the duration of vector-encoded gene expression. When injected into the brain, however, long-term expression is possible in spite of the ensuing inflammatory response. To examine the role of T cells in...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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1996
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| _version_ | 1826305492548321280 |
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| author | Byrnes, A Wood, M Charlton, H |
| author_facet | Byrnes, A Wood, M Charlton, H |
| author_sort | Byrnes, A |
| collection | OXFORD |
| description | In many organs, E1-deleted human adenovirus vectors trigger antiviral T cell responses which limit the duration of vector-encoded gene expression. When injected into the brain, however, long-term expression is possible in spite of the ensuing inflammatory response. To examine the role of T cells in the immune response in the brain, monoclonal antibodies were used to systemically deplete CD4+ and/or CD8+ T cell subsets from mice at the time of vector injection. The early phase of the inflammatory response, characterized by high MHC I expression and recruitment of mononuclear cells, was unaffected by T cell depletion. Six days after injection, however, inflammation was markedly reduced by CD8-depletion and eliminated by CD4-depletion. Vector expression of the marker protein beta-galactosidase did not differ between depleted and undepleted mice. In contrast, when mice had been previously exposed to adenovirus vector in the periphery, beta-galactosidase expression in the brain was transient, showing that T cells can effectively target vector-transduced cells in this organ. We conclude that adenovirus vectors are able to achieve long-term expression in the brain because such a route of injection triggers an ineffective T cell response. |
| first_indexed | 2024-03-07T06:33:39Z |
| format | Journal article |
| id | oxford-uuid:f6e218a1-6731-441c-85f0-706dd3a3732f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:33:39Z |
| publishDate | 1996 |
| record_format | dspace |
| spelling | oxford-uuid:f6e218a1-6731-441c-85f0-706dd3a3732f2022-03-27T12:38:17ZRole of T cells in inflammation caused by adenovirus vectors in the brain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f6e218a1-6731-441c-85f0-706dd3a3732fEnglishSymplectic Elements at Oxford1996Byrnes, AWood, MCharlton, HIn many organs, E1-deleted human adenovirus vectors trigger antiviral T cell responses which limit the duration of vector-encoded gene expression. When injected into the brain, however, long-term expression is possible in spite of the ensuing inflammatory response. To examine the role of T cells in the immune response in the brain, monoclonal antibodies were used to systemically deplete CD4+ and/or CD8+ T cell subsets from mice at the time of vector injection. The early phase of the inflammatory response, characterized by high MHC I expression and recruitment of mononuclear cells, was unaffected by T cell depletion. Six days after injection, however, inflammation was markedly reduced by CD8-depletion and eliminated by CD4-depletion. Vector expression of the marker protein beta-galactosidase did not differ between depleted and undepleted mice. In contrast, when mice had been previously exposed to adenovirus vector in the periphery, beta-galactosidase expression in the brain was transient, showing that T cells can effectively target vector-transduced cells in this organ. We conclude that adenovirus vectors are able to achieve long-term expression in the brain because such a route of injection triggers an ineffective T cell response. |
| spellingShingle | Byrnes, A Wood, M Charlton, H Role of T cells in inflammation caused by adenovirus vectors in the brain. |
| title | Role of T cells in inflammation caused by adenovirus vectors in the brain. |
| title_full | Role of T cells in inflammation caused by adenovirus vectors in the brain. |
| title_fullStr | Role of T cells in inflammation caused by adenovirus vectors in the brain. |
| title_full_unstemmed | Role of T cells in inflammation caused by adenovirus vectors in the brain. |
| title_short | Role of T cells in inflammation caused by adenovirus vectors in the brain. |
| title_sort | role of t cells in inflammation caused by adenovirus vectors in the brain |
| work_keys_str_mv | AT byrnesa roleoftcellsininflammationcausedbyadenovirusvectorsinthebrain AT woodm roleoftcellsininflammationcausedbyadenovirusvectorsinthebrain AT charltonh roleoftcellsininflammationcausedbyadenovirusvectorsinthebrain |