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.
Newton
Katy R
KR
Rheumatology Unit, Institute of Child Health, UCL, London, UK. k.newton@ich.ucl.ac.uk
Sala-Soriano
Emma
E
Varsani
Hemlata
H
Stephenson
John R
JR
Goldblatt
David
D
Wedderburn
Lucy R
LR
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