Immune responses to adenoviral vectors during gene transfer in the brain.

Journal article

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.

Authors: Kajiwara, K; Byrnes, A; Charlton, H; Wood, M; Wood, K

• Journal: Human gene therapy
• Volume: 8
• Issue: 3
• Pages: 253-265
• Publication date: 1997-02-01
• DOI: 10.1089/hum.1997.8.3-253
• EISSN: 1557-7422
• ISSN: 1043-0342
• Language: English
• Keywords: Animals; Gene Transfer Techniques; Mice, Inbred C3H; Immunophenotyping; Brain; Immunohistochemistry; Mice; Inflammation; Lac Operon; Leukocytes; Flow Cytometry; Male; Brain Chemistry; Genetic Vectors; Adenoviridae