title: Experimental autoimmune encephalomyelitis on the SJL mouse: effect of gamma delta 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 gamma delta T cells significantly reduced clinical and pathological signs of disease, which was associated with reduced expression of IL-1 beta, IL-6, TNF-alpha, and lymphotoxin at disease onset and a more persistent reduction in IFN-gamma. In this study, we analyzed the effect of gamma delta T cell depletion on chemokine and chemokine receptor expression. In the CNS of control EAE mice, mRNAs for RANTES, eotaxin, macrophage-inflammatory protein (MIP)-1 alpha, MIP-1 beta, 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 gamma delta 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-1 alpha and monocyte chemoattractant protein-1 at disease onset in gamma delta 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 gamma delta T cells reduced expression of CCR1 and CCR5 at disease onset only. We conclude that gamma delta T cells contribute to the development of EAE by promoting an inflammatory environment that serves to accelerate the inflammatory process in the CNS.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rajan
authors.forename: V C
authors.initials: VC
authors.lastname: Asensio
authors.forename: I L
authors.initials: IL
authors.lastname: Campbell
authors.forename: C F
authors.initials: CF
authors.lastname: Brosnan
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000737:chemistry / Q000276:immunology; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D006224:Cricetinae; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D019402:Macrophage Inflammatory Proteins / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D054407:Chemokine CCL4; D019742:Chemokines, CC; D007074:Immunoglobulin G; D019402:Macrophage Inflammatory Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019707:Receptors, Chemokine