Chemokine Regulation of Immune-mediated Demyelinating Disease.
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ Th1-mediated demyelinating disease of the central nervous system (CNS), which serves as a model for multiple schlerosis (MS). A hallmark in the pathogenesis of this disease is the emigration of T cells and monocytes from the blood to the CNS. Chemokines are small-molecular-weight chemotactic peptides, which are ligands for seven transmembrane-spanning, G protein-coupled receptors and which deliver signals leading to a variety of T cell functions including costimulation, cytokine expression, differentiation, and integrin activation. Several considerations suggest a role for chemokines in the influx of inflammatory cells to the CNS and the resulting disease process, including a tight temporal expression pattern with a relation to disease activity and prevention of disease development by in vivo neutralization. This article reviews the evidence that temporal and spatial expressions of chemokines are critical factors that regulate EAE, which makes this an appropriate animal model to study the pathogenesis of MS disease activity.
Karpus
William J.
WJ
Department of Pathology, Northwestern University Medical School, Chicago, Illinois, USA.
Kennedy
Kevin J.
KJ
Fife
Brian T.
BT
Hoffman
Lisa M.
LM