Thorsten R. Mempel
Massachusetts General Hospital
Center for Immunology and Inflammatory Diseases
Bldg. 149, 13th Street, Room 6222
Charlestown, MA 2129
Lab Members: 4 Postdoctoral Fellows
Our group studies how cell migration and cellular interactions regulate immune cell communication. In particular, we are interested to understand how cognate interactions of T lymphocytes with various types of antigen presenting cells regulate their functions in vivo.
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 dynamics of this process in vivo. Currently we are studying the interaction of cytotoxic T cells with antigen-presenting cells at effector sites, and how these interactions facilitate the signals that regulate the execution of T cell effector functions, such as cytokine release or cytotoxicity. For this purpose we are using advanced imaging techniques, such as multiphoton intravital microscopy (MP-IVM), which allow us not only to observe the migration of immune cells in their physiological tissue context in living anaesthetized mice, but also to monitor the activities of various signaling pathways and how these are regulated by intercellular contacts. Ultimately, integrating the analysis of signaling cascades with the observation of cellular interactions in vivo will provide us with a better understanding of the highly complex dynamic processes by which immune responses are regulated.
A second focus of our lab has become how certain pathogens not only evade, but also even exploit the immune system for their own benefit. Our main interest in this regard is HIV-1, a retrovirus that infects CD4+ cells of the human immune system. We have started to use mice with human immune systems, which are susceptible to infection with HIV-1, in order to investigate by MP-IVM in what ways the migration and cell-cell interactions of HIV-infected cells contribute to the systemic dissemination and persistence of HIV infection.
Mempel TR, Henrickson SE, von Andrian UH. T cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 2004; 427: 154-159.
Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, Boehmer H, von Andrian UH. Regulatory T cells reversibly suppress CD8 killer cell function independent of effector differentiation. Immunity 2006; 25(1): 129-141.
Pittet MJ, Mempel TR: Regulation of T Cell Migration and Effector Functions - Insights from in vivo imaging studies. Immunol. Rev. 2008; Feb; 221:107-29
Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler R, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ (2009). Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009; 325(5940): 612-6
Mempel TR, Bauer CA: Intravital imaging of T cell function in cancer. Clin Exp. Metastasis 2009; 26: 311-27, 2009
Last Update: 1/6/2014