Page 3 - ISNI abstracts

International Joint Israel-Greek-Italian Neuroimmunological meeting From Anti VLA-4 therapy to chemokine based potentiation of Tregs for treating MS Gizi Wildbaum and Nathan Karin Department of Immunology, bRappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9697, Haifa 31096, Israel About 23 years ago we (NK) together with Lawrence Steinman and Ted Yednock identified the alpha-4 beta-1 integrin (VLA-4) as the key adhesion molecule that drives the migration of T cells and monocytic cell to the inflamed central nervous system (CNS) in a set-up of experimental autoimmune encephalomyelitis (EAE), serving as a model for Multiple Sclerosis (MS), and that a monoclonal antibody (mAb) that binds the alpha-4 chain of VLA-4 could effectively suppress the disease. The humanized version of this particular antibody became the first approved biological drug for MS, and still is one the leading drugs in the field. As chemokines are the key activators of this molecule we became interest in exploring their role in autoimmunity, and later in cancer diseases. The major question we attempted to address has been why of so many chemokines (about 50 binding 20 receptors) there are only few that could serve as targets for effective therapy of inflammatory autoimmunity. We found that few chemokines, which we designated as “driver chemokines” not only attract leukocytes to inflammatory sites, but also later direct their biological properties. The current review focuses on the interplay between three ligands: CXCL9, CXCL10 and CXCL11 binding the same receptor (CXCR3) on CD4+ T cells, yet direct different signaling cascades to shape T cell mediated immunity. The review brings about a new concept about the biological activities of chemokines in shaping CD4+ T cell immunity, and also a new approach for applying chemokine based therapy of autoimmune diseases. . 3