| Autor: |
Newton KR; Rheumatology Unit, Institute of Child Health, UCL, London, UK. k.newton@ich.ucl.ac.uk, Sala-Soriano E, Varsani H, Stephenson JR, Goldblatt D, Wedderburn LR |
| Jazyk: |
angličtina |
| Zdroj: |
Immunology [Immunology] 2008 Dec; Vol. 125 (4), pp. 469-79. Date of Electronic Publication: 2008 May 28. |
| DOI: |
10.1111/j.1365-2567.2008.02860.x |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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