Combined Triggering of Dendritic Cell Receptors Results in Synergistic Activation and Potent Cytotoxic Immunity

摘要: Elimination of malignant cells and intracellular infections involves collaboration between CTLs Th1 inflammation. Dendritic drive this response via costimulation cytokines. We have defined key signals required for the exponential expansion specific CD8 + T in vivo mice. Immunization with two or more TLR agonists, anti-CD40, IFN-γ, surfactant were sufficient to unprecedented levels peptide protein Ag highly polarized CD4 responses. CD40 signaling was but could be provided by a concomitant Th place anti-CD40. Triggering these pathways activated migration activation myeloid plasmacytoid dendritic secretion IL-12. Cross-presentation can thus exploited induce potent cytotoxic responses long-term memory peptide/protein Ags. When combined tumor-associated from tyrosinase-related 2, our adjuvant approach effectively halted tumor growth an melanoma model effective than anti-CD40 single agonist. Antitumor immunity associated long-lived effector naturally processed presented Ag, protection partially not entirely dependent on cells. This flexible strategy is existing adjuvants provides technological platform rapid vaccine development.