CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce polyfunctional T-cell responses in nonhuman primates

Gabrielle Romain, Ellen van Gulck, Olivier Epaulard, Sangkon Oh, Dapeng Li, Gerard Zurawski, Sandra Zurawski, Antonio Cosma, Lucille Adam, Catherine Chapon, Biliana Todorova, Jacques Banchereau, Nathalie Dereuddre-Bosquet, Guido Vanham, Roger Le Grand, Frédéric Martinon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The pivotal role of DCs in initiating immune responses led to their use as vaccine vectors. However, the relationship between DC subsets involved in antigen presentation and the type of elicited immune responses underlined the need for the characterization of the DCs generated in vitro. The phenotypes of tissue-derived APCs from a cynomolgus macaque model for human vaccine development were compared with ex vivo-derived DCs. Monocyte/macrophages predominated in bone marrow (BM) and blood. Myeloid DCs (mDCs) were present in all tested tissues and were more highly represented than plasmacytoid DCs (pDCs). As in human skin, Langerhans cells (LCs) resided exclusively in the macaque epidermis, expressing CD11c, high levels of CD1a and langerin (CD207). Most DC subsets were endowed with tissue-specific combinations of PRRs. DCs generated from CD34 + BM cells (CD34-DCs) were heterogeneous in phenotype. CD34-DCs shared properties (differentiation and PRR) of dermal and epidermal DCs. After injection into macaques, CD34-DCs expressing HIV-Gag induced Gag-specific CD4 + and CD8 + T cells producing IFN-γ, TNF-α, MIP-1β, or IL-2. In high responding animals, the numbers of polyfunctional CD8 + T cells increased with the number of booster injections. This DC-based vaccine strategy elicited immune responses relevant to the DC subsets generated in vitro.

Original languageEnglish (US)
Pages (from-to)2019-2030
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • Antigen presenting cells
  • Dendritic cells
  • Immune responses
  • Vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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