title: The effect of gammadelta T cell depletion on cytokine gene expression in experimental allergic encephalomyelitis.
abstract: In experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, we showed previously that depletion of gammadelta T cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity. We now report on the effect of gammadelta T cell depletion on expression of five cytokine genes, IL-1, IL-6, TNF, lymphotoxin, and IFN-gamma in spinal cords of mice during the pre-onset, onset, height, and recovery phases of EAE, and on expression of type II nitric oxide synthase. In control animals, the mRNAs for IL-1 and IL-6 rose dramatically at disease onset and peaked before disease height, whereas the mRNAs for TNF, lymphotoxin, and IFN-gamma rose more slowly and peaked with peak of disease. In GL3-treated animals, a dramatic reduction in all five cytokines was noted at disease onset, but only IFN-gamma remained significantly reduced at a time point equivalent to height of disease in control animals. ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point. Studies of type II NOS also demonstrated a significant reduction in both mRNA and protein expression at the height of disease in GL3-treated animals. These results suggest that gammadelta T cells contribute to the pathogenesis of EAE by regulating the influx of inflammatory cells into the spinal cord and by augmenting the proinflammatory cytokine profile of the inflammatory infiltrates.
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: J D
authors.initials: JD
authors.lastname: Klein
authors.forename: C F
authors.initials: CF
authors.lastname: Brosnan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D051379:Mice; D009103:Multiple Sclerosis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse