PMID- 18510572
OWN - NLM
STAT- MEDLINE
DCOM- 20090220
LR  - 20211203
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 125
IP  - 4
DP  - 2008 Dec
TI  - Human dendritic cells infected with an adenoviral vector suppress proliferation 
      of autologous and allogeneic T cells.
PG  - 469-79
LID - 10.1111/j.1365-2567.2008.02860.x [doi]
AB  - 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.
FAU - Newton, Katy R
AU  - Newton KR
AD  - Rheumatology Unit, Institute of Child Health, UCL, London, UK. 
      k.newton@ich.ucl.ac.uk
FAU - Sala-Soriano, Emma
AU  - Sala-Soriano E
FAU - Varsani, Hemlata
AU  - Varsani H
FAU - Stephenson, John R
AU  - Stephenson JR
FAU - Goldblatt, David
AU  - Goldblatt D
FAU - Wedderburn, Lucy R
AU  - Wedderburn LR
LA  - eng
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080528
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Transforming Growth Factor beta)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Adenoviridae Infections/*immunology
MH  - Antibodies, Blocking/pharmacology
MH  - Cells, Cultured
MH  - Clonal Anergy
MH  - Culture Media, Conditioned
MH  - Cytokines/*immunology
MH  - Dendritic Cells/*immunology/*virology
MH  - Flow Cytometry
MH  - Genetic Vectors/administration & dosage
MH  - Humans
MH  - Immune Tolerance
MH  - Immunosuppression Therapy
MH  - Interleukin-10/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - T-Lymphocytes/*immunology
MH  - Transduction, Genetic/methods
MH  - Transforming Growth Factor beta/immunology
PMC - PMC2612560
EDAT- 2008/05/31 09:00
MHDA- 2009/02/21 09:00
PMCR- 2009/12/01
CRDT- 2008/05/31 09:00
PHST- 2008/05/31 09:00 [pubmed]
PHST- 2009/02/21 09:00 [medline]
PHST- 2008/05/31 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - IMM2860 [pii]
AID - 10.1111/j.1365-2567.2008.02860.x [doi]
PST - ppublish
SO  - Immunology. 2008 Dec;125(4):469-79. doi: 10.1111/j.1365-2567.2008.02860.x. Epub 
      2008 May 28.