The immune system is made up of specialized cells and tissues that act together to fight microbial infections and survey the body for malignant transformation. Immune responses are highly orchestrated and dynamic events that largely rely on the ability of immune cells to migrate in organs and tissues, to interact with each other in order to exchange information and to engage target cells in tissues to fulfill their effector functions. Natural killer and T lymphocytes are two key players of the host responses to pathogens and to some tumors and belong to the innate and adaptive arm of the immune system, respectively. The formation of cell-cell contacts represents a key event for T cell and NK cell to receive activation signal and exert effector functions. Ultimately, the efficiency of immune responses is critically dependent on the regulation and outcome of these contacts. We aim to launch a new generation of intravital microscopy that will allow us to move beyond the descriptive and towards functional imaging studies so we can get the ability to analyze, not only cellular behaviors, but also the signals and outcome of interactions established by T cells and NK cells in vivo. We will link key parameters regulating contact formation during T cell activation by dendritic cells, including calcium elevation, immunological synapse formation and contact stability in order to determine how they act together to influence T cell fate. In addition, we will further develop our projects on disease pathogenesis with the aim of gaining new knowledge on tumor immunity and parasitic infections. Identifying the parameters that regulate lymphocyte contact formation and outcome in these contexts will undoubtedly help delineate basic principles to improve strategies to treat cancer and infectious diseases.