Thorsten R. Mempel
Our group studies how cell migration organizes the communication between the innate and the adaptive immune systems. Specifically, we are interested in understanding how T lymphocytes traffic between lymphoid and non-lymphoid tissues and position themselves within these tissue environments to interact with various types of antigen-presenting cells (APC) to receive the instructive and selective cues that guide their development and regulate their differentiation into effector cells.
It is well established that interactions of naïve T cells with antigen-presenting dendritic cells in secondary lymphoid organs initiate T cell responses, and we have previously characterized the cellular dynamics of this process in vivo. Currently we are examining the interactions of cytotoxic T lymphocytes (CTL) with antigen-presenting cells at immune effector sites, such as tumor tissue, and how the stability, duration, and frequency of these interactions impinge on the coordinated activation of various signaling pathways in CTL that regulate their gene expression patterns and thus the quality and duration of the effector response as well as the formation of tissue-based immunological memory. We are also investigating how interactions of regulatory T cells with APC at effector sites not only regulate their local accumulation and functional activity, but also mediate their suppressive activity on effector T cells by altering APC functions. To study these processes in vivo, we are using multiphoton intravital microscopy (MP-IVM) approaches, which allow us not only to observe at the single cell level the migration of immune cells in their physiological tissue context in living anaesthetized mice, but at the same time to also monitor the activities of various intracellular signaling pathways and how these are controlled by intercellular contacts. Ultimately, integrating the analysis of dynamic gene activation processes and of the cellular interactions that drive these in vivo will provide us with a better understanding of the highly complex processes by which immune responses are regulated.
A second interest of our lab has become how some pathogens not only evade, but also exploit physiological properties of the immune system for their own benefit. Our current focus in this regard is on HIV-1, a retrovirus that infects human CD4+ cells. We have started to use MP-IVM in mice with human immune systems that are susceptible to infection with HIV-1 in order to investigate the ways by which this virus utilizes T cell – APC and T cell – T cell interactions, as well as the migratory properties of its target cells in order to initially take hold at mucosal transmission sites and then spread to and within other lymphoid and non-lymphoid tissues to generate a persistent systemic infection.
Center for Immunology and Inflammatory Diseases
Bldg. 149, 13th Street, Room 6222
Charlestown, MA 2129