CpG-C ISS-ODN activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of IFN-γ-secreting SIV-specific T cells
Teleshova,Natalia; Kenney,Jessica; Jones,Jennifer; Marshall,Jason; Van Nest,Gary; Dufour,Jason; Bohm,Rudolf; Lifson,Jeffrey D.; Gettie,Agegnehu; Pope,Melissa
Journal of Immunology 173(3): 1647-1657
Publication date: 2004
There are two principle subsets of dendritic cells (DCs); CD11cCD123 myeloid DCs (MDCs) and CD11cCD123 plasmacytoid DCs (PDCs). DC activation via TNF-TNFRs (e.g., CD40L) and TLRs (e.g., immunostimulatory oligodeoxyribonucleotides (ISS-ODNs)) is crucial for maximal stimulation of innate and adaptive immunity. Macaque DC biology is being studied to improve HIV vaccines using the SIV macaque model. Using lineage (Lin) markers to exclude non-DCs, LinHLA-DRCD11cCD123 MDCs and LinHLA-DRCD11cCD123 PDCs were identified in the blood of uninfected macaques and healthy macaques infected with SIV or simian-human immunodeficiency virus. Overnight culture of DC-enriched Lin-depleted cells increased CD80 and CD86 expression. IL-12 production and CD80/CD86 expression by MDC/PDC mixtures was further enhanced by CD40L and ISS-ODN treatment. A CpG-B ISS-ODN increased CD80/CD86 expression by PDCs, but resulted in little IFN-α secretion unless IL-3 was added. In contrast, a CpG-C ISS-ODN and aldrithiol-2-inactivated (AT-2) SIV induced considerable PDC activation and IFN-α release without needing exogenous IL-3. The CpG-C ISS-ODN also stimulated IL-12 release (unlike AT-2 SIV) and augmented DC immunostimulatory activity, increasing SIV-specific T cell IFN-? production induced by AT-2 SIV-presenting MDC/PDC-enriched mixtures. These data highlight the functional capacities of MDCs and PDCs in naive as well as healthy, infected macaques, revealing a promising CpG-C ISS-ODN-driven DC activation strategy that boosts immune function to augment preventative and therapeutic vaccine efficacy.