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 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.
Byrnes
A P
AP
Department of Human Anatomy, University of Oxford, UK.
Wood
M J
MJ
Charlton
H M
HM
D000260:Adenoviruses, Human / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D003342:Corpus Striatum / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase