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-Inducible Protein 10 Redirects Antigen-Specific T Cell Polarization and Suppresses Experimental Autoimmune Encephalomyelitis1
* Department of Immunology and
Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
IFN-
-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.
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