The immune system has evolved to protect the host from invasion of pathogens. A heterogeneous family of phagocytic leukocytes called dendritic cells (DC) form sentinel networks throughout the body to detect and induce immune responses against pathogens and to maintain tolerance toward self. DC have the unique ability to expand and modulate the function of antigen-specific T cells. There are several different populations of DC in human, each with apparently distinct functions. Understanding how the functions of these distinct DC populations are expressed and regulated is one of the main focuses of the Antigen Presentation Laboratory.

The Antigen Presentation Laboratory has been examining how several broad categories of physiological stimuli, found at sites of infection and inflammation, regulate DC function and influence their capacity to stimulate T cells. By understanding how to regulate DC function one can more effectively modulate T cell immune responses especially in the setting of cancer immunotherapy. The categories of physiological stimuli being studied include: (1) pro-inflammatory mediators (e.g. IL-1b, IL-6, TNF-a, IFN-a, IFN-g, IL-10), chemokines and bi-products of the arachidonic acid pathway (e.g. PGE2); (2) pathogen-derived signals (e.g. bacteria, viruses and their products); (3) T cell mediated signals (e.g. CD40 ligand); (4) Adenyl nucleotides (e.g. ATP, UTP, ADP) and their bi-products (e.g. Adenosine); and (5) synthetic adjuvants (ISCOMATRIX® adjuvant, CpG, Imiquimod). The Antigen Presentation Laboratory has identified how specific stimuli regulate different functions (e.g. migration or cytokine secretion) in specific DC populations. Expression of these functions is important for the trafficking of DC to lymphoid tissues where antigen-specific T cells reside as well as in T cell expansion and expression of effector function. The Antigen Presentation Laboratory has also identified that different populations of DC respond differently to these categories of physiological stimuli.

Thus, it now appears that not all DC populations or stages of maturation are destined to migrate to lymphoid organs and that the sequence in which stimuli are encountered significantly affects which DC functions are expressed. This highlights that immature DC may have multiple developmental options once recruited from the resting precursor pool. The Antigen Presentation Laboratory is now focussed on the consequences of modulating DC function upon their ability to induce T cell responses and whether these distinct DC populations can cross present antigen to CD8+ T cells. This research directly influences the DC clinical laboratory and how best to manipulate DC ex vivo for optimal vaccine delivery in cancer patients.

For current Ludwig student projects: Phd & Honours.