The activation of adaptive immune responses is critically dependent upon the activation of innate immune cells and mediators. However, the precise innate signals and pathways that best negotiate the transition from innate to adaptive have yet to be elucidated. A number of years of work have made it clear that the stimulation of innate pathways is alone insufficient for the eventual production of adaptive cellular immunity. Mere stimulation of the one or more innate receptors does not recapitulate the bulk of the infectious process that leads to potent adaptive immunity. Collectively the field has arrived at the conclusion that inflammation alone is a necessary, but insufficient, component of the eventual production of cellular immunity.
Our lab is interested in this curious boundary between the innate and adaptive immune systems and seeks to elucidate signals and pathways emanating from the various families of innate receptors most efficiently mediate the transition to the adaptive cellular immune response. In doing so, we seek to determine not only the basic rules of immunity, many of which remain elusive, but also to identify practical methods of intervention for the purposes of vaccine discovery, development and design. Experimentally we have demonstrated a number of ways in which the innate pathways intersect with the TNF receptor/Ligand superfamily, resulting in potent T cell expansion, effector function, and memory generation. These discoveries and novel vaccination methods are being applied to both viral and tumor model systems in an effort to develop clinically relevant methods of therapeutic vaccination against diseases such as chronic infections and cancer.