AUTOREACTIVE LYMPHOCYTES-T IN MULTIPLE-SCLEROSIS DETERMINED BY ANTIGEN-INDUCED SECRETION OF INTERFERON-GAMMA

被引:333
作者
OLSSON, T
ZHI, WW
HOJEBERG, B
KOSTULAS, V
JIANG, YP
ANDERSON, G
EKRE, HP
LINK, H
机构
[1] KAROLINSKA INST,CTR BIOTECHNOL,S-14186 HUDDINGE,SWEDEN
[2] KABI BIOPHARMA,RES & DEV IMMUNOBIOL,STOCKHOLM,SWEDEN
关键词
autoimmunity; cerebrospinal fluid; demyelination;
D O I
10.1172/JCI114800
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-γ 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 2.7-5.2/105 PBL from MS patients. MBP-reactive T cells were still more frequent among mononuclear cells isolated from the cerebrospinal fluid (CSF; 185/105 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.
引用
收藏
页码:981 / 985
页数:5
相关论文
共 45 条
[21]   VACCINATION AGAINST EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS WITH T-CELL RECEPTOR PEPTIDES [J].
HOWELL, MD ;
WINTERS, ST ;
OLEE, T ;
POWELL, HC ;
CARLO, DJ ;
BROSTOFF, SW .
SCIENCE, 1989, 246 (4930) :668-670
[22]   CELL-MEDIATED-IMMUNITY TO MYELIN-ASSOCIATED GLYCOPROTEIN, PROTEOLIPID PROTEIN, AND MYELIN BASIC-PROTEIN IN MULTIPLE-SCLEROSIS [J].
JOHNSON, D ;
HAFLER, DA ;
FALLIS, RJ ;
LEES, MB ;
BRADY, RO ;
QUARLES, RH ;
WEINER, HL .
JOURNAL OF NEUROIMMUNOLOGY, 1986, 13 (01) :99-108
[23]   An electrophoretic study of the protein components in cerebrospinal fluid and their relationship to the serum proteins [J].
Kabat, EA ;
Moore, DH ;
Landow, H .
JOURNAL OF CLINICAL INVESTIGATION, 1942, 21 (05) :571-577
[24]  
KABILAN L, 1990, IN PRESS EUR J IMMUN
[25]  
KIES MW, 1959, ALLERGIC ENCEPHALOMY, P293
[26]  
LEES MB, 1982, SCAND J IMMUNOL, V15, P147
[27]   ANTI-IDIOTYPIC NETWORK INDUCED BY T-CELL VACCINATION AGAINST EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS [J].
LIDER, O ;
RESHEF, T ;
BERAUD, E ;
BENNUN, A ;
COHEN, IR .
SCIENCE, 1988, 239 (4836) :181-183
[28]   INVITRO SYNTHESIS OF IMMUNOGLOBULINS AND AUTOANTIBODIES BY LYMPHOCYTES FROM VARIOUS BODY COMPARTMENTS DURING CHRONIC RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS [J].
OLSSON, T ;
HENRIKSSON, A ;
LINK, H .
JOURNAL OF NEUROIMMUNOLOGY, 1985, 9 (05) :293-305
[29]   ANTIMYELIN BASIC-PROTEIN AND ANTIMYELIN ANTIBODY-PRODUCING CELLS IN MULTIPLE-SCLEROSIS [J].
OLSSON, T ;
BAIG, S ;
HOJEBERG, B ;
LINK, H .
ANNALS OF NEUROLOGY, 1990, 27 (02) :132-136
[30]   TREATMENT OF MULTIPLE-SCLEROSIS WITH GAMMA-INTERFERON - EXACERBATIONS ASSOCIATED WITH ACTIVATION OF THE IMMUNE-SYSTEM [J].
PANITCH, HS ;
HIRSCH, RL ;
SCHINDLER, J ;
JOHNSON, KP .
NEUROLOGY, 1987, 37 (07) :1097-1102