title: T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis.
abstract: The pathogenesis of multiple sclerosis (MS) is believed to involve an autoimmune component directed against the myelin sheath. One potential target Ag for such autoimmune attack is the myelin-oligodendrocyte glycoprotein (MOG) because an anti-MOG mAb has profound influence on the course of experimental autoimmune encephalomyelitis, which to some extent represents an experimental model of MS. Using single cell assays, we have evaluated T and B cell reactivities to MOG in MS patients and controls. T cell reactivity was estimated by counting the number of cells that secreted IFN-gamma in response to MOG, whereas B cell reactivity was estimated by enumerating cells secreting antibodies that bound to MOG. MOG reactive T cells were detected in the peripheral blood of the majority of the 16 MS patients examined (mean 1/7299 mononuclear cells), but infrequently and at lower numbers in samples from neurologic controls. MOG-reactive T cells were more frequent among MS patients' cerebrospinal fluid (CSF) mononuclear cells (mean 1/450 cells). The T cell response to MOG was evidently MHC class II restricted, because Fab fragments of a rabbit polyclonal anti HLA-DR antibodies abrogated the Ag-induced increase in number of cells that secreted IFN-gamma, as analyzed on CSF and PBMC from three patients with MS. Anti-MOG IgG antibody-secreting cells were detected in blood in 8 of 16 MS patients (mean 1/25,641 cells), but they were also strongly accumulated in CSF, being detected in 8 of 10 MS patients examined (mean 1/265 cells), while rarely found in controls. The findings imply that MOG may represent a pathogenetically important target Ag in MS.
authors.affiliation: Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: B G
authors.initials: BG
authors.lastname: Xiao
authors.forename: G
authors.initials: G
authors.lastname: Andersson
authors.forename: H P
authors.initials: HP
authors.lastname: Ekre
authors.forename: C
authors.initials: C
authors.lastname: Linington
authors.forename: P
authors.initials: P
authors.lastname: Diener
mesh_terms: D000328:Adult; D000921:Antibody-Producing Cells / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D009185:Myelin Proteins; D007371:Interferon-gamma