J Immunol 2003 Feb 1;170(3):1274-1282
Denkinger CM, Denkinger M, Kort JJ, Metz C, Forsthuber TG.
Institute of Pathology, School of Medicine, Case Western Reserve University, and. Department of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106. Institute of Virology and Immunology, University of Wurzburg, Wurzburg, Germany. Picower Institute for Medical Research, Manhasset, NY 11030.
Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T cell activation.
However, its role in the pathogenesis of T cell-mediated autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), has remained unresolved.
In this study, we report that anti-MIF Ab treatment of SJL mice with acute EAE improved the disease severity and accelerated the recovery.
Furthermore, the anti-MIF treatment impaired the homing of neuroantigen-reactive pathogenic T cells to the CNS in a VCAM-1-dependent fashion.
Interestingly, MIF blockade also decreased the clonal size of the neuroantigen-specific Th1 cells and increased their activation threshold.
Taken together, the results demonstrate an important role for MIF in the pathogenesis of EAE/multiple sclerosis and suggest that MIF blockade may be a promising new strategy for the treatment of multiple sclerosis.