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Lack of phenotypic and functional impairment in dendritic cells from chimpanzees chronically infected with hepatitis C virus
- Source :
- Journal of virology. 78(12)
- Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- CD4-Positive T-Lymphocytes
Pan troglodytes
CD14
Hepatitis C virus
Immunology
Antigen presentation
Immunoglobulins
Hepacivirus
Biology
CD8-Positive T-Lymphocytes
medicine.disease_cause
Lymphocyte Activation
Microbiology
Virus
Antigens, CD
Virology
medicine
Animals
Humans
Antigen Presentation
CD40
Membrane Glycoproteins
hemic and immune systems
Cell Differentiation
Dendritic cell
Dendritic Cells
Hepatitis C, Chronic
Disease Models, Animal
Phenotype
Insect Science
biology.protein
Leukocytes, Mononuclear
Cytokines
Pathogenesis and Immunity
Antibody
CD8
Subjects
Details
- ISSN :
- 0022538X
- Volume :
- 78
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....6ad6b514ade2890b7b6981e62ed2fc64