Induction of immunological tolerance to adenoviral vectors by using a novel dendritic cell-based strategy.

ABSTRACT: The success of helper-dependent adenoviral (HD-Ad) vector-mediated lung gene therapy is hampered by the host immune response, which limits pulmonary transgene expression following multiple rounds of vector readminstration. Here, we show that HD-Ad-mediated pulmonary gene expression is sustained even upon three rounds of readministration to immunodeficient mice, highlighting the need to suppress the adaptive immune response for sustained gene expression following vector readministration. Therefore, we devised a dendritic cell (DC)-based strategy for induction of immunological tolerance toward HD-Ad vectors. DCs derived in the presence of interleukin-10 (IL-10) are refractory to HD-Ad-induced maturation and instead facilitate generation of IL-10-producing Tr1 regulatory T cells which suppres

SUBMITTER: Kushwah R 

PROVIDER: S-EPMC3302513 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature