Role of T cells in inflammation caused by adenovirus vectors in the brain

Abstract

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.