A role for macrophage inflammatory protein-3 alpha/CC chemokine ligand 20 in immune priming during T cell-mediated inflammation of the central nervous system.
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)-3alpha/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-3alpha, 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-3alpha 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-3alpha coincided with onset of clinical disease. Treatment of mice with specific neutralizing anti-MIP-3alpha 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-3alpha was not essential for the effector phase of EAE. Together, these data demonstrate that MIP-3alpha plays a critical role in the sensitization phase of EAE.
Kohler
Rachel E
RE
Department of Molecular Biosciences, University of Adelaide, Adelaide, South Australia, Australia.
Caon
Adriana C
AC
Willenborg
David O
DO
Clark-Lewis
Ian
I
McColl
Shaun R
SR
D000818:Animals; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007114:Immunization / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000276:immunology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D007106:Immune Sera; D019402:Macrophage Inflammatory Proteins; D018991:Myelin Proteolipid Protein; D054399:Receptors, CCR6; D019707:Receptors, Chemokine