טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentNavon Osnat
SubjectApplying Naked DNA Vaccines Encoding the CXCR6 Chemokine
Receptor for the Therapy of T Cell Mediated
Autoimmunity
DepartmentDepartment of Biotechnology
Supervisor Professor Nathan Karin


Abstract

EAE is an autoimmune disease of the CNS that serves as a model in rodents for the human disease Multiple Sclerosis. During EAE, TH cells have been characterized as regulators of the cellular inflammatory response and B cell maturation.

CXCR6 is expressed on CD8+, CD4+ T cells, and plasma cells, and mediates migration of TH1 cells to the inflammation site in the CNS. It's ligand CXCL16 is expressed on dendritic cells and monocytes/macrophages. MBP-specific CD4+ effector TH1 cells producing IFN-g over-express CXCR6. Our research examined the involvement of this receptor-ligand interaction in the regulation of the autoimmune inflammatory process in EAE.

EAE was induced in Lewis rats, followed by immunization with several rounds of DNA encoding CXCR6. These rats developed a shorter and less severe form of EAE compared with the control groups.

Assuming the naked DNA vaccine encoding CXCR6 caused breakdown of immunological tolerance against the receptor, we conducted additional experiments to verify the production of high antibody titers specific for CXCR6 in the sera collected from the DNA-immunized rats. We were unsuccessful in transfer of immunological tolerance to CXCR6 by IgG antibodies. In some experiments there was a dramatic increase in IgM specific for the receptor. In these experiments we also witnessed a distinct depletion of the CD4+ T cell population in draining lymph nodes of the injection site.

The team is currently working on mechanisms to explain the depletion in CD4+ T cell population, concentrating on the role of CD8+ T cells in immunological tolerance breakdown.