Immunological memory —the ability to remember and respond rapidly and more vigorously to a pathogen upon subsequent encounters— is a fundamental property of the immune system conveyed by subsets of white blood cells called B and T cells. Mesenchymal stromal cells (MSCs) in the bone marrow and peripheral lymphoid organs are known to promote T cell memory by organizing pro-survival niches but the precise mechanisms by which they support T cell longevity is still not clearly understood.
Thanks to the German Research Foundation funds, Prof. Gattinoni – Chair of Functional Immune Cell Modulation at the University of Regensburg – will explore the ground-breaking idea that MSCs may promote the development and long-term persistence of memory T cells by donating their mitochondria and subsequently changing T cell metabolism. Gattinoni’s group has recently found that MSCs can transfer their mitochondria to CD8+ T cells in a dish, improving their metabolic fitness and function. Whether mitochondrial transfer from MSC to CD8+ T cells happens during immune responses to pathogens and with which consequences is what the Gattinoni team will determine during this project.
“The findings from these studies will redefine our understanding of how MSCs and stromal niches control the generation and maintenance of immunological memory.” says Jeremy Baldwin, the postdoctoral scientist in the Gattinoni laboratory who will lead the project. The work also aims to unravel the mechanisms that drive mitochondrial transfer and to exploit this knowledge to artificially increase mitochondrial transfer for future therapeutic applications. “The new biology discovered will have major implications for the development of novel vaccination strategies against pathogens and foster radical innovation in the design of new T cell-based cancer immunotherapies.” says Prof. Gattinoni.
Leibniz Institute for immunotherapy and University of Regensburg as an ideal setting
The Gattinoni laboratory is embedded in the new Leibniz Institute for immunotherapy (LIT). The LIT offers the ideal setting for the Reinhart Koselleck project since it is fully dedicated to the development of immunotherapies with a strong focus on T cell therapies. Its cutting-edge instrumentation and the proximity to the University of Regensburg’s vivarium and live-imaging facilities will enable to pursue successfully this ambitious project.
“This research can open new horizons in intercellular communication biology and pioneer the development of a new field of organelle therapeutics” says Prof. Philipp Beckhove. Professor Udo Hebel, the President of the University of Regensburg further underlines “For two years in a row, the University of Regensburg is receiving this prestigious grant award. This emphasizes once more our ability to attract top scientists and to provide an excellent scientific environment for them to succeed.”
About the Reinhart Koselleck Project
This DFG program enables researchers with an outstanding scientific track-record to pursue exceptionally innovative, higher-risk projects that cannot be funded within the scope of other DFG programs or within the framework of the applicant’s own institution. The prestigious and rarely granted award is named after Reinhart Koselleck, who was a “lateral thinker” and one of the most important German historians of the 20th century.