Identifying the functional outcome of different antigen presenting cells for NKT cell activation in the liver.

NKT cells are a unique immune cell type that show great promise in cancer immunotherapy.
However, clinical application is hampered by both the production of cytokines with opposing effects
on the immune system and the induction of anergy, a hyporesponsiveness that prevents repeated
activation of NKT cells. There is evidence suggesting that these limitations are related to the nature
of the antigen presenting cell that activates the NKT cell. However, too little is known about which
antigen presenting cells are relevant for an optimal effector outcome, as many studies rely on in
vitro work or flawed mouse models. We will therefore investigate in detail which antigen
presenting cells are important in vivo for inducing a Th1-polarized cytokine response in NKT cells of
the liver without inducing anergy. We will use novel Cre mouse lines that are available to us
through collaborators for selective depletion of the antigen presenting molecule CD1d in specific cell
types, as well as state-of-the art techniques such as multiphoton intravital microscopy to get a
detailed readout of NKT cell activation over time.