A Role for Macrophage Inflammatory Protein-3(Beta Symbol)/CC chemokine Ligand 20 in Immune Priming During T Cell-Mediated Inflammation of the Central Nervous System

Abstract

Chemokines are a family of cytokines that exhibit selective chemoattractant properties for target leukocytes and play a significant role in leukocyte migration. In this study, we have investigated the role of the C-C chemokine, macrophage inflammatory protein (MIP)-3α/CC chemokine ligand 20, in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of T cell-dependent inflammation. Expression in the CNS of MIP-3α, as determined by RT-PCR, increased in a time-dependent manner such that peak expression correlated with peak clinical disease. Similarly, levels of immunoreactive MIP-3α in the draining lymph nodes increased up to 10-fold 9 days postimmunization and remained elevated for up to 21 days postimmunization. The increased production of MIP-3α coincided with onset of clinical disease. Treatment of mice with specific neutralizing anti- MIP-3α Abs significantly reduced the severity of both clinical EAE and neuroinflammation by inhibiting the sensitization of lymphocytes to the specific Ag and release of lymphocytes from the draining lymph nodes. In contrast, adoptive transfer experiments indicated that MIP-3α was not essential for the effector phase of EAE. Together, these data demonstrate that MIP-3α plays a critical role in the sensitization phase of EAE. Show more