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Impact of T cell - dendritic cell interactions on the clearance of a persistent viral infection
Antragstellerin
Dr. Jasmin Herz
Fachliche Zuordnung
Immunologie
Förderung
Förderung von 2010 bis 2012
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 167139709
Several viral pathogens can persistently infect the central nervous system (CNS) in humans resulting health problems. Immunotherapy is a successful approach to treat animal models of persistent infection and has also shown promise in humans. To understand the mechanism(s) by which immunotherapy of adoptively transferred virus-specific memory T cells completely purge viruses from CNS neurons in the absence of cellular damage, our laboratory studies a mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection. Using this model we recently observed that dendritic cells (DCs) were recruited into the brain of persistently infected mice and were capable of inducing memory T cells to release anti-viral cytokines ex vivo. These DCs were found to be required for successful immunotherapy. Presently, the mechanism by which DCs facilitate the success of adoptive immunotherapy is not known. I hypothesize that CNS-infiltrating DCs serve as a local accessory cell population which supports therapeutic memory T lymphocytes by promoting survival, cell division, and anti-viral activities. During my fellowship period, I will use intravital two-photon microscopy, in combination with cellular and molecular approaches, to provide the first real time mechanistic insights into the coordinated movements and interactions of DCs and T lymphocytes within the CNS during immunotherapy.
DFG-Verfahren
Forschungsstipendien
Internationaler Bezug
USA
Gastgeber
Professor Dr. Dorian B. McGavern