Impact of co-stimulatory signals on recruitment and kinetics of antigen-specific cytotoxic T-lymphocytes in vivo

• Applicant: Dr. Jan Rohr
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 187640750

Infectious diseases still pose a major disease burden for mankind, particularly for children. This can at least in part be attributed to the fact that for several life-threatening infectious diseases vaccine development has thus far been unsuccessful. Within the planned research I will address how different factors control the magnitude of pathogen-specific cytotoxic T cell responses, and knowledge of these factors will be of value for the more rational development of future vaccines. Specifically, I will determine how the recruitment of naïve T cells, how T cell proliferation and how T cell death shape the magnitude of antigen-specific T cell responses. Furthermore, I will assess how different co-stimulatory signals influence T cell recruitment, proliferation or death. To address these fundamental immunological questions I will exploit an innovative technology termed cellular barcoding that was recently developed by the host lab. In addition, I will develop a novel method, allowing to determine the relative contribution of cell proliferation and cell death in an expanding (T) cell population in vivo. By determining how three very basic factors regulate the development of antigen-specific T cell responses under different conditions, this project will contribute to the our understanding of both pathogen and vaccine-induced T cell responses. In addition, the technology that this project will deliver should be of value to assess in vivo cell death in a variety of biologically relevant settings.

• DFG Programme: Research Fellowships
• International Connection: Netherlands
• Host: Professor Ton Schumacher