Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.
Multiple sclerosis (MS) is a disease with unknown cause characterized by inflammation and demyelination in the central nervous system. Although an autoimmune pathogenesis has been suggested, there are no conclusive data on the number of T cells autoreactive with myelin antigens in MS compared to controls. We showed that T lymphocytes secreting interferon-gamma in response to possible target autoantigens are severalfold more common among PBL mononuclear cells in patients with MS than in patients with aseptic meningitis and tension headache. On average T cells reactive with myelin basic protein (MBP), two different MBP peptides, or with proteolipid protein amounted to 2.7-5.2/10(5) PBL from MS patients. MBP-reactive T cells were still more frequent among mononuclear cells isolated from the cerebrospinal fluid (CSF; 185/10(5) CSF cells). We concluded that T cells reactive with myelin autoantigens are strongly increased in MS. This approach to detect them could allow definition of immunodominant T cell epitopes in individual MS patients, and thereby enable further development towards specific immunotherapy.
Olsson
T
T
Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Zhi
W W
WW
Höjeberg
B
B
Kostulas
V
V
Jiang
Y P
YP
Anderson
G
G
Ekre
H P
HP
Link
H
H
D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology; D018991:Myelin Proteolipid Protein; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D007371:Interferon-gamma