Research Group
- Dr. Matthias W. Hoffmann, Principal Investigator
- Prof. Reinhold Förster, Co-Investigator
Location
- Medizinische Hochschule Hannover, Hannover, Germany
Title
- Chemokines and their Receptors as Therapeutic Targets to Prevent Allograft Rejection
T lymphocytes play a central role in the rejection of organ allografts. To be activated, antigen-unexperienced (naive) T lymphocytes migrate to secondary lymphoid organs, such as lymph nodes, the spleen, Peyer’s patches, or tonsils. There, naive T lymphocytes are activated by antigen-presenting cells that carry foreign antigens from the graft to these secondary lymphoid organs. Since migration of naive T lymphocytes to secondary lymphoid organs critically depends on chemotactic lymphokines (chemokines), one strategy to block T lymphocyte activation consists of the blockade of these chemokines or their receptors.
The chemokine receptor required for migration of naive T lymphocytes into secondary lymphoid organs is CCR7. Therefore, the main topic of the research proposal will be to study to what extent allogeneic skin and heart grafts will be accepted in CCR7-deficient mice, and how this is effected. These results will be used to develop therapeutic strategies to prevent the rejection of organ allografts at a very early point in T cell activation. This treatment strategy would spare the immunosuppression of beneficial antigen-experienced (memory) T lymphocytes and would maintain their anti-bacterial, anti-viral or anti-tumour activities.
In summary, this research proposal aims to develop a novel type of immunosuppression that specifically targets the organ allograft, without suppressing beneficial T cells reactive to pathogens or tumour cells.
