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© Research
Publication : AIDS (London, England)

Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-alpha are potent inducers of HIV-specific CD8 T cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in AIDS (London, England) - 15 Aug 2003

Carbonneil C, Aouba A, Burgard M, Cardinaud S, Rouzioux C, Langlade-Demoyen P, Weiss L

Link to Pubmed [PMID] – 12891059

AIDS 2003 Aug;17(12):1731-40

OBJECTIVE: To investigate the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-alpha to induce the differentiation of peripheral monocytes into dendritic cells (DC) and their ability to trigger an HIV-specific CD8 T-cell response.

METHODS: Monocytes isolated from both seronegative controls and HIV-infected individuals were differentiated into DC using GM-CSF with either IL-4 or IFN-alpha for 7 days. We assessed the phenotypic characteristics and IL-12 production by flow cytometry. The ability of DC to trigger CD8 T-cell responses was assessed by means of ELISpot and cytotoxicity assays. In addition, HIV-1-RNA levels were measured in culture supernatants.

RESULTS: Compared with control DC generated in the presence of GM-CSF and IL-4, DC generated in the presence of GM-CSF and IFN-alpha expressed higher levels of MHC class I molecules and produced similar or higher levels of IL-12 after CD40 ligation or Staphyloccus aureus Cowan stimulation. GM-CSF/IFN-alpha DC expressed low levels of CD4, CXCR4 and DC-SIGN and did not produce detectable virus during the differentiation period. Pulsed GM-CSF/IFN-alpha DC were found to prime CD8 T cells from HIV-negative controls to exert cytotoxic activity against target cells expressing HIV antigens. HIV peptide-pulsed GM-CSF/IFN-alpha DC promote specific IFN-gamma production by autologous CD8 T cells from HIV-seronegative donors. Furthermore, GM-CSF/IFN-alpha DC from HIV-seropositive patients efficiently present HIV peptides to autologous CD8 T lymphocytes.

CONCLUSION: GM-CSF and IFN-alpha allow the generation of DC with high CD8 T-cell stimulating abilities. Therefore, this strategy may represent a novel approach to therapeutic vaccination in HIV disease.

http://www.ncbi.nlm.nih.gov/pubmed/12891059