PMID- 20713888
OWN - NLM
STAT- MEDLINE
DCOM- 20101123
LR  - 20100903
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 6
DP  - 2010 Sep 15
TI  - Directly transfected langerin+ dermal dendritic cells potentiate CD8+ T cell 
      responses following intradermal plasmid DNA immunization.
PG  - 3463-71
LID - 10.4049/jimmunol.1001825 [doi]
AB  - Dendritic cells (DCs) play a critical role in CD8(+) T cell priming following DNA 
      vaccination. In contrast to other DNA injection routes or immunization with viral 
      vectors, Ag presentation is delayed following needle injection of plasmid DNA 
      into the skin. The contribution of various skin DC subsets to this process is not 
      known. In this study, we show that dermal CD11c(+) cells are the most important 
      transgene-expressing cells following immunization. Using langerin- diphtheria 
      toxin receptor mice we demonstrated that langerin(+) dermal DCs (Ln(+) dDCs) were 
      crucial for generating an optimal CD8(+) T cell response. Blocking migration of 
      skin cells to the lymph node (LN) ablated immunogenicity, suggesting that 
      migration of dDC subsets to the LN is essential for generating immunity. This 
      migration generated a weak Ag-presenting activity in vivo until day 5 
      postimmunization, which then increased dramatically. We further found that Ln(+) 
      dDCs and dDCs were the only DC populations directly presenting Ag to CD8(+) T 
      cells ex vivo during the initial 8-d period postimmunization. This activity 
      changed on the following days, when both skin DCs and LN-resident DCs were able 
      to present Ag to CD8(+) T cells. Taken together, our in vivo and ex vivo results 
      suggest that activation of CD8(+) T cells following intradermal plasmid DNA 
      immunization depends on directly transfected Ln(+)dDCs and dDCs. Moreover, the 
      type of DCs presenting Ag changed over time, with Ln(+)dDCs playing the major 
      role in potentiating the initial CD8(+) T cell response.
FAU - Elnekave, Mazal
AU  - Elnekave M
AD  - Institute of Dental Sciences, Hebrew University-Hadassah School of Dental 
      Medicine, Jerusalem, Israel.
FAU - Furmanov, Karina
AU  - Furmanov K
FAU - Nudel, Itay
AU  - Nudel I
FAU - Arizon, Moran
AU  - Arizon M
FAU - Clausen, Bjorn E
AU  - Clausen BE
FAU - Hovav, Avi-Hai
AU  - Hovav AH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100816
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Surface)
RN  - 0 (Cd207 protein, mouse)
RN  - 0 (DNA, Viral)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose-Binding Lectins)
SB  - IM
MH  - Adenoviruses, Human/genetics/immunology
MH  - Animals
MH  - Antigen Presentation/genetics/immunology
MH  - Antigens, Surface/*biosynthesis/*genetics
MH  - Biolistics
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism/virology
MH  - Cells, Cultured
MH  - DNA, Viral/administration & dosage/*immunology
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - *Gene Knock-In Techniques
MH  - Humans
MH  - Injections, Intradermal
MH  - Lectins, C-Type/*biosynthesis/*genetics
MH  - Lymphocyte Activation/genetics/immunology
MH  - Mannose-Binding Lectins/*biosynthesis/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Plasmids/administration & dosage/immunology
MH  - Skin/cytology/*immunology/metabolism
MH  - Transfection/*methods
EDAT- 2010/08/18 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/08/18 06:00
PHST- 2010/08/18 06:00 [entrez]
PHST- 2010/08/18 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - jimmunol.1001825 [pii]
AID - 10.4049/jimmunol.1001825 [doi]
PST - ppublish
SO  - J Immunol. 2010 Sep 15;185(6):3463-71. doi: 10.4049/jimmunol.1001825. Epub 2010 
      Aug 16.