PMID- 14551149
OWN - NLM
STAT- MEDLINE
DCOM- 20040310
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 3
DP  - 2004 Feb 1
TI  - Highly efficient expression of transgenic proteins by naked DNA-transfected 
      dendritic cells through terminal differentiation.
PG  - 811-9
AB  - Dendritic cells (DCs) play a key role in the induction and control of immunity. 
      Genetic engineering of DCs is a promising approach for the development of a broad 
      range of immunomodulatory strategies, for purposes ranging from genetic 
      immunization to tolerance induction. The development of DC-based immunotherapies 
      is limited by the inability to efficiently transfect DCs using naked DNA. Here we 
      demonstrate that after plasmid DNA delivery, the transgene expression level 
      controlled by the human immediate-early cytomegalovirus promoter (hIE-CMVp) is 
      higher in mature DCs than in immature DCs and is further increased after terminal 
      differentiation of DCs by agonist anti-CD40 monoclonal antibody (mAb) or after DC 
      interaction with CD4(+) T cells. CD40 signaling of DCs resulted in nuclear 
      translocation of the transcription factors nuclear factor-kappaB (NF-kappaB), 
      activator of protein-1 (AP-1), and cyclic adenosine monophosphate 
      (cAMP)-responsive element, necessary for the activation of hIE-CMVp. Transgene 
      expression by DCs diminished after the inhibition of these transcription factors 
      or the blockade of adhesion molecules involved in the DC-T-cell synapse. 
      Importantly, CD40 signaling of DCs results in the highly efficient expression and 
      presentation of transgenic antigens and the induction of "in vivo" cytotoxic 
      T-cell (CTL) responses specific for transgenic antigen peptides, demonstrating 
      the functional potential of genetically engineered DCs.
FAU - Larregina, Adriana T
AU  - Larregina AT
AD  - W1051 Biomedical Science Tower, 200 Lothrop St, Pittsburgh, PA 15213, USA. 
      adrianal@pitt.edu
FAU - Morelli, Adrian E
AU  - Morelli AE
FAU - Tkacheva, Olga
AU  - Tkacheva O
FAU - Erdos, Geza
AU  - Erdos G
FAU - Donahue, Cara
AU  - Donahue C
FAU - Watkins, Simon C
AU  - Watkins SC
FAU - Thomson, Angus W
AU  - Thomson AW
FAU - Falo, Louis D Jr
AU  - Falo LD Jr
LA  - eng
GR  - P01 AI0550794/AI/NIAID NIH HHS/United States
GR  - P01 CA73743/CA/NCI NIH HHS/United States
GR  - R01 AI41011/AI/NIAID NIH HHS/United States
GR  - R01 AI43916/AI/NIAID NIH HHS/United States
GR  - R01 DK49745/DK/NIDDK NIH HHS/United States
GR  - R21 AI55027/AI/NIAID NIH HHS/United States
GR  - R21 HL69725/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031009
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens)
RN  - 0 (CD40 Antigens)
RN  - 0 (DNA, Recombinant)
RN  - 0 (Recombinant Proteins)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens
MH  - CD40 Antigens/metabolism
MH  - Cell Differentiation
MH  - Cytomegalovirus/genetics
MH  - DNA, Recombinant/*genetics
MH  - Dendritic Cells/*cytology/immunology/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - Immunotherapy/methods
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Ovalbumin/immunology
MH  - Promoter Regions, Genetic
MH  - Recombinant Proteins/*genetics
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2003/10/11 05:00
MHDA- 2004/03/11 05:00
CRDT- 2003/10/11 05:00
PHST- 2003/10/11 05:00 [pubmed]
PHST- 2004/03/11 05:00 [medline]
PHST- 2003/10/11 05:00 [entrez]
AID - S0006-4971(20)50211-5 [pii]
AID - 10.1182/blood-2003-02-0524 [doi]
PST - ppublish
SO  - Blood. 2004 Feb 1;103(3):811-9. doi: 10.1182/blood-2003-02-0524. Epub 2003 Oct 9.