Human dendritic cells infected with an adenoviral vector suppress proliferation of autologous and allogeneic T cells.
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.
Rheumatology Unit, Institute of Child Health, UCL, London, UK. k.newton@ich.ucl.ac.uk
Katy R
KR
Newton
Emma
E
Sala-Soriano
Hemlata
H
Varsani
John R
JR
Stephenson
David
D
Goldblatt
Lucy R
LR
Wedderburn
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000276:immunology*; D019138:Antibodies, Blocking / Q000494:pharmacology; D002478:Cells, Cultured; D017635:Clonal Anergy; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods; D016212:Transforming Growth Factor beta / Q000276:immunology
D019138:Antibodies, Blocking; D017077:Culture Media, Conditioned; D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10