Dendritic Cell Biology

Dr. Gunn’s lab has two major lines of research directly applicable to vaccine development. His team is determining how antigen presenting cells act to regulate the strength, duration and character of immune response. This work focuses on the identification, isolation, and characterization of specific dendritic cell subtypes in mice. The lab was the first to describe murine plasmacytoid dendritic cells (PDC), which correspond to an unusual DC type previously found only in humans. This allowed, for the first time, experimental manipulation of this cell type in vivo. PDC appear to play a major role in anti-viral immunity for several reasons. They are highly responsive to viral stimulation and are the predominant source of type I interferons, a family of cytokines that act to control viral infection. Virus-activated PDC also stimulate anti-viral CD8~T cell activity. Importantly, in the absence of viral infection, PDC appear to inhibit immune responses. For these reasons, the activation of PDC represents a key control point in turning off immune regulatory mechanisms that are normally present and turning on robust anti-viral immune responses. This makes them an important target for vaccine and adjuvant development. Current work in Dr. Gunn’s lab involves determining the exact functions of PDC in vivo, identifying the mechanisms by which they send and receive signals, and better defining their role in regulating pathogen-specific immune responses.

Our understanding of how immune responses are regulated at the DC level has led Dr. Gunn’s team to the development of agents that can stimulate or inhibit specific immune responses. They now know that effective vaccine development will involve the identification of agents and adjuvants that stimulate particular DC responses while inhibiting normal counter-regulatory mechanisms. This, in turn, can lead to the development of immune responses that are specific for a particular pathogen, rather than the more generic immune responses that are induced by current adjuvants.