Plasmid DNA encoding IFN-gamma-inducible protein 10 redirects antigen-specific T cell polarization and suppresses experimental autoimmune encephalomyelitis

• Published in: The Journal of immunology (1950) Vol. 168; no. 11; pp. 5885 - 5892
• Main Authors: Wildbaum, Gizi, Netzer, Nir, Karin, Nathan
• Format: Journal Article
• Language: English
• Published: United States 01-06-2002
• Subjects: Animals; Antibody Formation; Cell Line; Cell Polarity; Chemokine CXCL10; Chemokines, CXC - genetics; Chemokines, CXC - immunology; CpG Islands - physiology; Cytokines - biosynthesis; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Female; Genetic Therapy; Plasmids; Rats; Rats, Inbred Lew; T-Lymphocytes - physiology; Th1 Cells - physiology; Th2 Cells - physiology; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.11.5885

IFN-gamma-inducible protein 10 (IP-10) is a CXC chemokine that stimulates the directional migration of activated T cells, particularly Th1 cells. We demonstrate in this work that during activation this chemokine drives naive CD4(+) T cells into Th1 polarization. Administration of plasmid DNA encoding self IP-10 was found capable of breaking down immunological tolerance to IP-10, resulting in the generation of self-specific immunity to the gene product of the vaccine. Despite the CpG motif that drives T cells into Th1, the vaccine redirected the polarization of myelin basic protein-specific T cells into Th2 and conferred the vaccinated recipients a high state of resistance against experimental autoimmune encephalomyelitis, a T cell-mediated autoimmune disease of the CNS. The vaccine also suppressed full-blown ongoing disease in a mouse model of multiple sclerosis. Self-specific Ab to IP-10 developed in protected animals could inhibit leukocyte migration, alter the in vitro Th1/Th2 balance of autoimmune T cells, and adoptively transfer disease suppression. This demonstrates not only the pivotal role of a chemokine in T cell polarization and function but also its potential implications for plasmid DNA gene therapy.