PMID- 15163708
OWN - NLM
STAT- MEDLINE
DCOM- 20040629
LR  - 20231213
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 78
IP  - 12
DP  - 2004 Jun
TI  - Lack of phenotypic and functional impairment in dendritic cells from chimpanzees 
      chronically infected with hepatitis C virus.
PG  - 6151-61
AB  - Dendritic cells (DCs), which are potent antigen-presenting cells (APCs), are used 
      as adjuvants for the treatment of cancer and infectious diseases in human and 
      nonhuman primates, with documented clinical efficacy. The hepatitis C virus 
      (HCV)-chimpanzee model is the best available model for testing the 
      immunotherapeutic effects of DCs in the setting of a chronic infection, as 
      chimpanzees develop a persistent infection resembling that seen in humans. 
      However, several reports have suggested that DCs derived from chronically 
      infected individuals or nonhuman primates are functionally compromised. As a 
      prelude to clinical studies, we evaluated whether functionally mature DCs could 
      be generated in chimpanzee plasma by good manufacturing practice using CD14(+) 
      mononuclear precursors from chronically infected chimpanzees. DCs generated in a 
      medium with HCV-negative plasma and treated with a defined cocktail of cytokines 
      or a CD40 ligand trimer matured fully, as measured by the induction of CD83 
      expression and the upregulation of costimulatory molecules. Furthermore, the 
      expression of CCR7 was induced, suggesting an acquisition of migration capacity. 
      Mature DCs were capable of stimulating allogeneic T cells, antigen-specific 
      memory CD4(+) T cells, and HCV-specific CD8(+)-T-cell clones. In all cases, there 
      was no evidence of HCV infection in DCs. Furthermore, these DCs maintained their 
      phenotype and APC function after cryopreservation. Finally, no discernible 
      differences were noted between DCs derived from HCV-infected and uninfected 
      chimpanzees. In summary, precursor cells from HCV-infected chimpanzees are fully 
      capable of differentiating into functional, mature DCs, which can now be 
      reproducibly prepared for investigations of their immunotherapeutic potential in 
      the setting of chronic HCV infection.
FAU - Larsson, Marie
AU  - Larsson M
AD  - New York University School of Medicine, New York, NY 10016, USA. 
      larssm01@med.nyu.edu
FAU - Babcock, Ethan
AU  - Babcock E
FAU - Grakoui, Arash
AU  - Grakoui A
FAU - Shoukry, Naglaa
AU  - Shoukry N
FAU - Lauer, Georg
AU  - Lauer G
FAU - Rice, Charles
AU  - Rice C
FAU - Walker, Christopher
AU  - Walker C
FAU - Bhardwaj, Nina
AU  - Bhardwaj N
LA  - eng
GR  - R01 AI044628/AI/NIAID NIH HHS/United States
GR  - AI 44628/AI/NIAID NIH HHS/United States
GR  - U19 AI 48231/AI/NIAID NIH HHS/United States
GR  - CA 57973/CA/NCI NIH HHS/United States
GR  - U19 AI048231/AI/NIAID NIH HHS/United States
GR  - AI 40034/AI/NIAID NIH HHS/United States
GR  - R01 AI 47367/AI/NIAID NIH HHS/United States
GR  - R37 AI044628/AI/NIAID NIH HHS/United States
GR  - R01 CA057973/CA/NCI NIH HHS/United States
GR  - R01 AI047367/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens, CD
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Differentiation
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/*physiology
MH  - Disease Models, Animal
MH  - Hepacivirus/*immunology
MH  - Hepatitis C, Chronic/*immunology/virology
MH  - Humans
MH  - Immunoglobulins/metabolism
MH  - Leukocytes, Mononuclear/cytology/immunology
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/metabolism
MH  - Pan troglodytes
MH  - Phenotype
MH  - CD83 Antigen
PMC - PMC416524
EDAT- 2004/05/28 05:00
MHDA- 2004/06/30 05:00
PMCR- 2004/06/01
CRDT- 2004/05/28 05:00
PHST- 2004/05/28 05:00 [pubmed]
PHST- 2004/06/30 05:00 [medline]
PHST- 2004/05/28 05:00 [entrez]
PHST- 2004/06/01 00:00 [pmc-release]
AID - 78/12/6151 [pii]
AID - 2403-03 [pii]
AID - 10.1128/JVI.78.12.6151-6161.2004 [doi]
PST - ppublish
SO  - J Virol. 2004 Jun;78(12):6151-61. doi: 10.1128/JVI.78.12.6151-6161.2004.