Immune responses to adenoviral vectors during gene transfer in the brain.
We have investigated the immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of adult mice. Injection of these nonreplicating vectors caused a marked inflammatory response in the brain as assessed by immunocytochemistry and flow cytometry of leukocytes....
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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1997
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| _version_ | 1797062120540471296 |
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| author | Kajiwara, K Byrnes, A Charlton, H Wood, M Wood, K |
| author_facet | Kajiwara, K Byrnes, A Charlton, H Wood, M Wood, K |
| author_sort | Kajiwara, K |
| collection | OXFORD |
| description | We have investigated the immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of adult mice. Injection of these nonreplicating vectors caused a marked inflammatory response in the brain as assessed by immunocytochemistry and flow cytometry of leukocytes. Infiltrating leukocytes were detectable within 2 days of injection and reached a maximum by 9 days. Thereafter, the number of infiltrating cells decreased, but a small number persisted in the brain until day 60. Between 2 and 4 days after injection, the percentage of CD8+ cells detectable increased whereas the percentage of CD4+ cells present in the infiltrating population did not significantly increase until day 6, peaking on day 15. Activated CD25+ T cells were detectable between days 6 and 15. beta-Galactosidase (beta-Gal), the product of the lacZ gene encoded by the vector, was also detected, both at the injection site in the striatum and also in the substantia nigra. Expression peaked between 4 and 6 days but a small number of beta-Gal+ cells was still seen at 60 days after injection. This study demonstrates that a quantitative analysis of the immune responses caused by a nonreplicating adenovirus vector is possible in the brain. E1-deleted adenoviral vectors trigger a strong inflammatory response in the brain, but this immune response is not sufficient to eliminate completely expression of genes encoded by the adenoviral construct. |
| first_indexed | 2024-03-06T20:41:01Z |
| format | Journal article |
| id | oxford-uuid:344958fb-6464-4494-ad1c-3f138931bc00 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:41:01Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:344958fb-6464-4494-ad1c-3f138931bc002022-03-26T13:25:02ZImmune responses to adenoviral vectors during gene transfer in the brain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:344958fb-6464-4494-ad1c-3f138931bc00EnglishSymplectic Elements at Oxford1997Kajiwara, KByrnes, ACharlton, HWood, MWood, KWe have investigated the immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of adult mice. Injection of these nonreplicating vectors caused a marked inflammatory response in the brain as assessed by immunocytochemistry and flow cytometry of leukocytes. Infiltrating leukocytes were detectable within 2 days of injection and reached a maximum by 9 days. Thereafter, the number of infiltrating cells decreased, but a small number persisted in the brain until day 60. Between 2 and 4 days after injection, the percentage of CD8+ cells detectable increased whereas the percentage of CD4+ cells present in the infiltrating population did not significantly increase until day 6, peaking on day 15. Activated CD25+ T cells were detectable between days 6 and 15. beta-Galactosidase (beta-Gal), the product of the lacZ gene encoded by the vector, was also detected, both at the injection site in the striatum and also in the substantia nigra. Expression peaked between 4 and 6 days but a small number of beta-Gal+ cells was still seen at 60 days after injection. This study demonstrates that a quantitative analysis of the immune responses caused by a nonreplicating adenovirus vector is possible in the brain. E1-deleted adenoviral vectors trigger a strong inflammatory response in the brain, but this immune response is not sufficient to eliminate completely expression of genes encoded by the adenoviral construct. |
| spellingShingle | Kajiwara, K Byrnes, A Charlton, H Wood, M Wood, K Immune responses to adenoviral vectors during gene transfer in the brain. |
| title | Immune responses to adenoviral vectors during gene transfer in the brain. |
| title_full | Immune responses to adenoviral vectors during gene transfer in the brain. |
| title_fullStr | Immune responses to adenoviral vectors during gene transfer in the brain. |
| title_full_unstemmed | Immune responses to adenoviral vectors during gene transfer in the brain. |
| title_short | Immune responses to adenoviral vectors during gene transfer in the brain. |
| title_sort | immune responses to adenoviral vectors during gene transfer in the brain |
| work_keys_str_mv | AT kajiwarak immuneresponsestoadenoviralvectorsduringgenetransferinthebrain AT byrnesa immuneresponsestoadenoviralvectorsduringgenetransferinthebrain AT charltonh immuneresponsestoadenoviralvectorsduringgenetransferinthebrain AT woodm immuneresponsestoadenoviralvectorsduringgenetransferinthebrain AT woodk immuneresponsestoadenoviralvectorsduringgenetransferinthebrain |