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Toll-like receptor ...
Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses
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- Lore, K (author)
- Karolinska Institutet
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Betts, MR (author)
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Brenchley, JM (author)
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Kuruppu, J (author)
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Khojasteh, S (author)
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Perfetto, S (author)
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Roederer, M (author)
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Seder, RA (author)
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Koup, RA (author)
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(creator_code:org_t)
- The American Association of Immunologists, 2003
- 2003
- English.
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 171:8, s. 4320-4328
- Related links:
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http://www.jimmunol....
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http://kipublication...
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https://doi.org/10.4...
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Abstract
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- Optimal Ag targeting and activation of APCs, especially dendritic cells (DCs), are important in vaccine development. In this study, we report the effects of different Toll-like receptor (TLR)-binding compounds to enhance immune responses induced by human APCs, including CD123+ plasmacytoid DCs (PDCs), CD11c+ myeloid DCs (MDCs), monocytes, and B cells. PDCs, which express TLR7 and TLR9, responded to imidazoquinolines (imiquimod and R-848) and to CpG oligodeoxynucleotides stimulation, resulting in enhancement in expression of costimulatory molecules and induction of IFN-α and IL-12p70. In contrast, MDCs, which express TLR3, TLR4, and TLR7, responded to poly(I:C), LPS, and imidazoquinolines with phenotypic maturation and high production of IL-12 p70 without producing detectable IFN-α. Optimally TLR ligand-stimulated PDCs or MDCs exposed to CMV or HIV-1 Ags enhanced autologous CMV- and HIV-1-specific memory T cell responses as measured by effector cytokine production compared with TLR ligand-activated monocytes and B cells or unstimulated PDCs and MDCs. Together, these data show that targeting specific DC subsets using TLR ligands can enhance their ability to activate virus-specific T cells, providing information for the rational design of TLR ligands as adjuvants for vaccines or immune modulating therapy.
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- art (subject category)
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