The integrin alpha 4 (Itga4) is expressed on immune cells and is an important molecule for the migration of T cells in various organs. Because of this propriety, a monoclonal antibody specific to Itga4 is used for the treatment of multiple sclerosis (MS). Although effective, anti-Itga4 therapy has been associated with the development of progressive multifocal leukoencephalopathy (PML), a life threatening condition, which results from a rare infection of the central nervous system (CNS) by the JC virus. Despite its use and efficacy in the clinic, it remains unclear how different cells of the adaptive immune system are affected by Itga4 deletion or neutralization. Experimental autoimmune encephalomyelitis (EAE) serves as an animal model of multiple sclerosis (MS). It results from an autoimmune attack by myelin reactive effector T helper (Th) 1 and Th17 cells and progressive demyelination. Foxp3+ regulatory T cells can control effector T cell responses but are not always effective during autoimmune disease progression. Using mice with selective deletion of Itga4 in T cells, we previously reported that Itga4 selectively inhibits the migration of Th 1 cells but not Th17 cells in the CNS. We have now established that Itga4 differentially affect the migration of effector and regulatory T cells during EAE. The implication of our findings for MS therapy will be discussed.
- Copyright © 2013 by The American Association of Immunologists, Inc.