Human dendritic cells infected with an adenoviral vector suppress proliferation of autologous and allogeneic T cells


Newton, KR; Sala-Soriano, E; Varsani, H; Stephenson, JR; Goldblatt, D; Wedderburn, LR; (2008) Human dendritic cells infected with an adenoviral vector suppress proliferation of autologous and allogeneic T cells. Immunology, 125 (4). pp. 469-479. ISSN 0019-2805 DOI: https://doi.org/10.1111/j.1365-2567.2008.02860.x

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Abstract

Dendritic cells (DCs) play a key role in the type and course of an immune response. The manipulation of human DCs to produce therapeutic agents by transduction with viral vectors is a growing area of research. We present an investigation into the effects of adenoviral vector infection on human DCs and other cell types, and on their subsequent ability to induce T-cell proliferation. We show that infection with replication-deficient adenovirus results in impaired proliferation of T cells in a mixed lymphocyte reaction (MLR). We show this to be an active suppression rather than a defect in the DCs as T cells also fail to proliferate in response to phytohaemagglutinin in the presence of adenoviral vector-infected DCs. This suppression is not attributable to phenotypic changes, death or inability of the DCs to produce cytokines on stimulation. By separation of DCs from T cells, and addition of conditioned supernatants, we show that suppression is mediated by a soluble factor. Blocking of interleukin (IL)-10 but not transforming growth factor (TGF)-beta could overcome the suppressive effect in some donors, and the source of the suppressive IL-10 was lymphocytes exposed to conditioned supernatant. Together our data suggest that infection of DCs by adenoviral vectors leads to suppression of the resulting immune response.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 18510572
Web of Science ID: 260670500004
URI: http://researchonline.lshtm.ac.uk/id/eprint/6648

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