טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSalomon Izhar
SubjectTreatment of Adjuvant Induced Arthritis by Targeted Naked
DNA Encoding IP-10
DepartmentDepartment of Medicine
Supervisor Professor Nathan Karin


Abstract

Interferon gamma- inducible protein 10 (IP-10) a CXC chemokine that is thought to manifest a pro-inflammatory role because it stimulates the directional migration of activated T cells, particularly Th1 cells. It is an opened question whether this chemokine is also directly involved in T cell polarization. We have shown that during the course of Adjuvant Induced Arthritis the immune system mounts a notable antibody titer against self IP-10. Upon the administration of naked DNA encoding IP-10 this titer rapidly accelerates to provide protective immunity. Self-specific Ab to IP-10 developed in protected animals, as well as neutralizing Ab to IP-10 that we have generated in rabbits, could inhibit leukocyte migration, alter the in vivo and in vitro Th1/Th2 balance towards low IFN-g, low TNF-a high IL-4 producing T cells, and adoptively transfer disease suppression. This not only demonstrates the pivotal role of this chemokine in T cell polarization during experimentally induced arthritis but also suggests a practical way to interfere in the regulation of disease to provide protective immunity. From the basic science perspective this study challenges the paradigm of in vivo redundancy.  After all we did not neutralize the activity of other chemokines that bind CXCR3 (i.e. MIG and ITAC) and yet significantly blocked not only AA but also the in vivo competence to mount DTH.