Experimental Autoimmune Encephalomyelitis on the SJL Mouse: Effect of γδ T Cell Depletion on Chemokine and Chemokine Receptor Expression in the Central Nervous System

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system (CNS) that is a model for multiple sclerosis. Previously, we showed that depletion of γδ T cells significantly reduced clinical and pathological signs of disease, which was associated with reduced expression of IL-1β, IL-6, TNF-α, and lymphotoxin at disease onset and a more persistent reduction in IFN-γ. In this study, we analyzed the effect of γδ T cell depletion on chemokine and chemokine receptor expression. In the CNS of control EAE mice, mRNAs for RANTES, eotaxin, macrophage-inflammatory protein (MIP)-1α, MIP-1β, MIP-2, inducible protein-10, and monocyte chemoattractant protein-1 were detected at disease onset, increased as disease progressed, and fell as clinical signs improved. In γδ T cell-depleted animals, all of the chemokine mRNAs were reduced at disease onset; but at the height of disease, expression was variable and showed no differences from control animals. mRNA levels then fell in parallel with control EAE mice. ELISA data confirmed reduced expression of MIP-1α and monocyte chemoattractant protein-1 at disease onset in γδ T cell-depleted mice, and total T cell numbers were also reduced. In normal CNS mRNAs for CCR1, CCR3, and CCR5 were observed, and these were elevated in EAE animals. mRNAs for CCR2 were also detected in the CNS of affected mice. Depletion of γδ T cells reduced expression of CCR1 and CCR5 at disease onset only. We conclude that γδ T cells contribute to the development of EAE by promoting an inflammatory environment that serves to accelerate the inflammatory process in the CNS.