title: Decreased severity of myelin oligodendrocyte glycoprotein peptide 33 - 35-induced experimental autoimmune encephalomyelitis in mice with a disrupted TCR delta chain gene.
abstract: Immunization of C57BL / 6 mice with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35 - 55 induces chronic experimental autoimmune encephalomyelitis (EAE). The role of gamma delta T cells in the regulation of EAE is unclear. We investigated gamma delta T cells in C57BL / 6 wild-type mice and C57BL / mice with a disrupted TCRdelta chain gene (delta(- / -) mice) using MOG p35 - 55. We found significantly less disease in delta(- / -) mice immunized with MOG / complete Freund's adjuvant (mean maximal EAE score 4.3 +/- 0.8 in wild-type vs. 2.3 +/- 0.5 in delta(- / -) mice). Transfer of wild-type spleen cells restored the ability of delta(- / -) mice to develop equally severe EAE as wild-type mice. In addition to IFN-gamma, IL-2, IL-5 and IL-10 was decreased in delta(- / -) mice. Decreased immune responses were also seen in delta(- / -) animals immunized with OVA peptide or protein and in concanavalin A-stimulated splenocytes from delta(- / -) mice. Enriched dendritic cells from delta(- / -) mice secreted significantly less TNF-alpha in response to lipopolysaccharide stimulation. Furthermore, when EAE was induced by adoptive transfer of an anti-MOG p35 - 55 alpha beta T cell line, there was a striking reduction of disease incidence (0 %) and severity in delta(- / -) as compared to wild-type mice (83 % incidence). delta(- / -) mice showed no cellular infiltration in the spinal cord whereas wild-type animals had infiltration of macrophages, B cells, alpha beta- and gamma delta T cells. In adoptive transfer EAE, there was reduced IL-2 and IFN-gamma secretion in delta(- / -) mice. These results demonstrate an impaired immune response in the delta(- / -) mouse that is associated with a defect in developing both actively induced and adoptively transferred EAE.
authors.affiliation: Center for Neurologic Diseases Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Spahn
authors.forename: S
authors.initials: S
authors.lastname: Issazadah
authors.forename: A J
authors.initials: AJ
authors.lastname: Salvin
authors.forename: H L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D004679:Encephalomyelitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016692:Receptors, Antigen, T-Cell, gamma-delta