T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis

• Published in: The Journal of immunology (1950) Vol. 146; no. 5; pp. 1490 - 1495
• Main Authors: Sun, J, Link, H, Olsson, T, Xiao, BG, Andersson, G, Ekre, HP, Linington, C, Diener, P
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.03.1991; American Association of Immunologists
• Subjects: Adult; Antibody-Producing Cells - metabolism; B-Lymphocytes - immunology; Biological and medical sciences; Female; Humans; Immunoglobulin G - secretion; Interferon-gamma - secretion; Male; Medical sciences; Middle Aged; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin Proteins - immunology; Neurology; T-Lymphocytes - immunology; Human; Immunopathology; Multiple sclerosis; Nervous system diseases; Immune response; Myelin; Secretion; Cytokine; Autoantibody; Autoimmune disease; Glycoproteins; Cerebrospinal fluid; In vitro; Blood; Enumeration(counting); Inflammatory disease; B»-Lymphocyte; Oligodendrocyte; T-Lymphocyte; Gamma interferon
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.146.5.1490

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.