PMID- 20648001
OWN - NLM
STAT- MEDLINE
DCOM- 20110303
LR  - 20240508
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 11
DP  - 2010 Nov
TI  - Enhanced induction of HIV-specific cytotoxic T lymphocytes by dendritic 
      cell-targeted delivery of SOCS-1 siRNA.
PG  - 2028-37
LID - 10.1038/mt.2010.148 [doi]
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that play a critical 
      role in the activation of T cells. RNA interference (RNAi)-mediated silencing of 
      negative immunoregulatory molecules expressed by DCs may provide a strategy to 
      enhance the potency of DC-based vaccines and immunotherapy. Ablation of 
      suppressor of cytokine signaling-1 (SOCS-1) in antigen-presenting cells has been 
      shown to enhance cellular immune response in mice. Here, we used a previously 
      reported DC-targeting approach to deliver small interfering RNA (siRNA) against 
      SOCS-1 to human myeloid-derived DCs (MDDCs). SOCS1-silencing in MDDCs resulted in 
      enhanced cytokine responses to lipopolysaccharide (LPS) and a strong 
      mixed-lymphocyte reaction. Moreover, only DCs treated with SOCS-1 siRNA, and not 
      controls, elicited strong primary in vitro responses to well-characterized 
      HLA-A*0201-restricted Melan-A/MART-1 and human immunodeficiency virus (HIV) Gag 
      epitopes in naive CD8(+) T cells from healthy donors. Finally, stimulation of 
      CD8(+) T cells from HIV-seropositive subjects with SOCS1-silenced DCs resulted in 
      an augmented polyfunctional cytotoxic T-lymphocyte (CTL) response, suggesting 
      that SOCS-1 silencing can restore functionally compromised T cells in HIV 
      infection. Collectively, these results demonstrate the feasibility of 
      DC3-9dR-mediated manipulation of DC function to enhance DC immunogenicity for 
      potential vaccine or immunotherapeutic applications.
FAU - Subramanya, Sandesh
AU  - Subramanya S
AD  - Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, USA.
FAU - Armant, Myriam
AU  - Armant M
FAU - Salkowitz, Janelle R
AU  - Salkowitz JR
FAU - Nyakeriga, Alice M
AU  - Nyakeriga AM
FAU - Haridas, Viraga
AU  - Haridas V
FAU - Hasan, Maroof
AU  - Hasan M
FAU - Bansal, Anju
AU  - Bansal A
FAU - Goepfert, Paul A
AU  - Goepfert PA
FAU - Wynn, Katherine K
AU  - Wynn KK
FAU - Ladell, Kristin
AU  - Ladell K
FAU - Price, David A
AU  - Price DA
FAU - N, Manjunath
AU  - N M
FAU - Kan-Mitchell, June
AU  - Kan-Mitchell J
FAU - Shankar, Premlata
AU  - Shankar P
LA  - eng
GR  - R01 AI071882/AI/NIAID NIH HHS/United States
GR  - AI071882/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100720
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Cytokines)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SOCS1 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
SB  - IM
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology
MH  - Flow Cytometry
MH  - HIV/genetics/*immunology
MH  - HIV Infections/immunology/virology
MH  - HLA-A Antigens/immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Myeloid Cells/drug effects/immunology/metabolism
MH  - Peptide Fragments/pharmacology
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling Proteins/antagonists & 
      inhibitors/genetics/*metabolism
MH  - T-Lymphocytes/drug effects/*immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC2990509
EDAT- 2010/07/22 06:00
MHDA- 2011/03/04 06:00
PMCR- 2011/11/01
CRDT- 2010/07/22 06:00
PHST- 2010/07/22 06:00 [entrez]
PHST- 2010/07/22 06:00 [pubmed]
PHST- 2011/03/04 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - S1525-0016(16)30890-5 [pii]
AID - 10.1038/mt.2010.148 [doi]
PST - ppublish
SO  - Mol Ther. 2010 Nov;18(11):2028-37. doi: 10.1038/mt.2010.148. Epub 2010 Jul 20.