Document Type
Article
Publication Date
3-15-2004
Publication Title
The Journal of Experimental Medicine
Department
Geisel School of Medicine
Abstract
Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with CD40 stimulation, demonstrating that synergy with the CD40 pathway is a property of TLR-derived stimuli in general. The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNγ, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN. These studies provide the rational basis for the use of TLR and CD40 agonists together as essential adjuvants to optimize vaccines designed to elicit protective or therapeutic immunity.
DOI
10.1084/jem.20031591
Dartmouth Digital Commons Citation
Ahonen, Cory L.; Doxsee, Christie L.; McGurran, Sean M. M.; Riter, Tony R.; Wade, William F.; Barth, Richard J.; Vasilakos, John P.; Noelle, Randolph J.; and Kedl, Ross M., "Combined TLR and CD40 Triggering Induces Potent CD8+ T Cell Expansion with Variable Dependence on Type I IFN" (2004). Dartmouth Scholarship. 1156.
https://digitalcommons.dartmouth.edu/facoa/1156
