PMID- 20140891
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20100302
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Linking)
VI  - 12
IP  - 3
DP  - 2010 Mar
TI  - Dendritic cells lentivirally engineered to overexpress interleukin-10 inhibit 
      contact hypersensitivity responses, despite their partial activation induced by 
      transduction-associated physical stress.
PG  - 231-43
LID - 10.1002/jgm.1436 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) constitute an attractive target for 
      immunotherapeutic approaches. Because DCs are largely refractory to transfection 
      with plasmid DNA, several viral transduction protocols were established. The 
      potential side-effects of lentiviral transduction on the phenotype and activation 
      state of DCs left unstimulated after transduction have not been assessed. There 
      is a need to analyse these parameters as a result of the requirement of using DCs 
      with a low activation state for therapeutic strategies intended to induce 
      tolerance. METHODS: Lentivirally-transduced bone marrow (BM)-derived DCs (LV-DCs) 
      in comparison with mock-transduced (Mock-DCs) and untreated DCs were analysed 
      with regard to the induction of maturation processes on the RNA, protein and 
      functional level. BM-DCs engineered to overexpress interleukin (IL)-10 were 
      analysed for therapeutic potential in a mouse model of allergic contact 
      dermatitis. RESULTS: Compared with untreated DCs, Mock-DCs and LV-DCs displayed 
      an altered gene expression signature. Mock-DCs induced a stronger T cell 
      proliferative response than untreated DCs. LV-DCs did not further augment the T 
      cell proliferative response, but induced a slightly different T cell cytokine 
      pattern compared to Mock-DCs. Accordingly, the gene promoter of the DC maturation 
      marker fascin mediated efficient expression of the model transgene IL-10 in 
      unstimulated-transduced BM-DCs. Nevertheless, IL-10 overexpressing BM-DCs exerted 
      tolerogenic activity and efficiently inhibited the contact hypersensitivity 
      response in previously hapten-sensitized mice. CONCLUSIONS: Lentiviral 
      transduction of BM-DCs results in their partial activation. Nevertheless, the 
      transduction of these DCs with a vector encoding the immunomodulatory cytokine 
      IL-10 rendered them tolerogenic. Thus, lentivirally-transduced DCs expressing 
      immunomodulatory molecules represent a promising tool for induction of tolerance.
FAU - Besche, Verena
AU  - Besche V
AD  - University Medical Center of the Johannes Gutenberg-University, Clinical Research 
      Unit Allergology, Department of Dermatology, Mainz, Germany.
FAU - Wiechmann, Nadine
AU  - Wiechmann N
FAU - Castor, Timo
AU  - Castor T
FAU - Trojandt, Stefanie
AU  - Trojandt S
FAU - Hohn, Yvonne
AU  - Hohn Y
FAU - Kunkel, Hanna
AU  - Kunkel H
FAU - Grez, Manuel
AU  - Grez M
FAU - Grabbe, Stephan
AU  - Grabbe S
FAU - Reske-Kunz, Angelika B
AU  - Reske-Kunz AB
FAU - Bros, Matthias
AU  - Bros M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Dendritic Cells/*immunology/*transplantation
MH  - Dermatitis, Allergic Contact/*therapy
MH  - Female
MH  - Genetic Engineering
MH  - Immunotherapy
MH  - Interleukin-10/*genetics
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Stress, Physiological
MH  - T-Lymphocytes/*immunology
MH  - Transduction, Genetic
EDAT- 2010/02/09 06:00
MHDA- 2010/05/21 06:00
CRDT- 2010/02/09 06:00
PHST- 2010/02/09 06:00 [entrez]
PHST- 2010/02/09 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
AID - 10.1002/jgm.1436 [doi]
PST - ppublish
SO  - J Gene Med. 2010 Mar;12(3):231-43. doi: 10.1002/jgm.1436.