|Dendritic cells (DC) are the professional antigen presenting cells of the immune system that instruct and control the activation of B and T lymphocytes, the mediators of specific immunity. DC are highly mobile cells and by their sequential migration from peripheral tissues to lymphoid organs they serve as sentinels of the immune system. Their extremely potent capacity to initiate and modulate immunity is currently exploited to fight infectious and autoimmune diseases as well as cancer. It is now well established that multiple distinct DC subsets exist. Moreover, it is well appreciated that the DC subset and the microenvironment a DC encounters in the periphery, determine the type of immune response that is induced, ranging from a TH1 or TH2 response to regulatory T cells and immune tolerance. The purpose of this project is to investigate the potential of different DC-subsets to induce an effective CTL mediated anti-tumor immune response in vivo and to characterize the type and magnitude of the induced immune response. The plan of investigation consists of comparing DC-subsets with respect to their ability to:
1) migrate into lymphoid tissues and their localization within these tissues (using green fluorescent protem (GFP)-DC and Indium-111 labeled DC);
2) induce an immune response against the foreign antigen ovalbumin (OV A) or the self antigen Tyrosinase Related Protein-2 (TRP-2),
3) their vaccine efficacy in tumor models (B 16-OVA model and the fully autologous B 16- TRP-2 tumor model). We shall determine the quality and the magnitude of the induced responses using MHC-tetramers and cytokine assays.