Combined triggering of dendritic cell receptors results in synergistic activation and potent cytotoxic immunity

Wells, J. W., Cowled, C. J., Farzaneh, F. and Noble, A. (2008) Combined triggering of dendritic cell receptors results in synergistic activation and potent cytotoxic immunity. Journal of Immunology, 181 5: 3422-3431.

Author Wells, J. W.
Cowled, C. J.
Farzaneh, F.
Noble, A.
Title Combined triggering of dendritic cell receptors results in synergistic activation and potent cytotoxic immunity
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2008-09
Sub-type Article (original research)
Volume 181
Issue 5
Start page 3422
End page 3431
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Elimination of malignant cells and intracellular infections involves collaboration between CTLs and Th1 inflammation. Dendritic cells drive this response via costimulation and cytokines. We have defined key signals required for the exponential expansion of specific CD8+ T cells in vivo in mice. Immunization with two or more TLR agonists, anti-CD40, IFN-γ, and surfactant were sufficient to drive unprecedented levels of CD8 response to peptide or protein Ag and highly polarized Th1 CD4 responses. CD40 signaling was required for CD8 expansion but could be provided by a concomitant CD4 Th response in place of anti-CD40. Triggering of these pathways activated migration and activation of myeloid and plasmacytoid dendritic cells and secretion of IL-12. Cross-presentation can thus be exploited to induce potent cytotoxic responses and long-term memory to peptide/protein Ags. When combined with a tumor-associated peptide from tyrosinase-related protein 2, our combined adjuvant approach effectively halted tumor growth in an in vivo melanoma model and was more effective than anti-CD40 and a single TLR agonist. Antitumor immunity was associated with long-lived effector memory CD8 cells specific for the naturally processed and presented tumor Ag, and tumor protection was partially but not entirely dependent on CD8 T cells. This flexible strategy is more effective than existing adjuvants and provides a technological platform for rapid vaccine development.
Keyword Cd8 T-Cells
Tyrosinase-Related Protein-2
In-Vivo
Cross-Presentation
Cpg-Dna
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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