THE ROLE OF T-CELLS IN MULTIPLE-SCLEROSIS - IMPLICATIONS FOR THERAPIES TARGETING THE T-CELL RECEPTOR

被引:24
作者
UTZ, U
MCFARLAND, HF
机构
[1] Neuroimmunology Branch, NINDS, National Institutes of Health, Bethesda, MD
关键词
DEMYELINATION; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE SCLEROSIS; T CELL RECEPTORS; T LYMPHOCYTES;
D O I
10.1097/00005072-199407000-00005
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The cause of multiple sclerosis (MS) is unknown, but an immunopathological process with both endogenous and exogenous factors contributing to disease seems likely. Considerable recent attention, triggered predominantly by findings in the animal model, experimental allergic encephalomyelitis (EAE), which resembles MS, has focused on the role of T cells in MS. Findings in the animal model have raised the possibility that demyelination could be produced by CD4+ T cells specific for myelin proteins and expressing a limited set of T cell receptor (TCR) molecules. Thus, specific therapies targeting T cells or more specifically the TCR could represent an effective treatment of MS as has been demonstrated in EAE. However, current studies of patients with MS indicate that the immunological mechanisms in MS are considerably more complicated than in EAE. The evidence for a pivotal role for T cells in MS and the characteristics of these T cells particularly with respect to TCR usage and potential for therapies directed at the TCR will be examined in this review.
引用
收藏
页码:351 / 358
页数:8
相关论文
共 74 条
[1]   LIMITED HETEROGENEITY OF T-CELL RECEPTORS FROM LYMPHOCYTES MEDIATING AUTOIMMUNE ENCEPHALOMYELITIS ALLOWS SPECIFIC IMMUNE INTERVENTION [J].
ACHAORBEA, H ;
MITCHELL, DJ ;
TIMMERMANN, L ;
WRAITH, DC ;
TAUSCH, GS ;
WALDOR, MK ;
ZAMVIL, SS ;
MCDEVITT, HO ;
STEINMAN, L .
CELL, 1988, 54 (02) :263-273
[2]   T-CELLS RESPONSIVE TO MYELIN BASIC-PROTEIN IN PATIENTS WITH MULTIPLE-SCLEROSIS [J].
ALLEGRETTA, M ;
NICKLAS, JA ;
SRIRAM, S ;
ALBERTINI, RJ .
SCIENCE, 1990, 247 (4943) :718-721
[3]   SUSCEPTIBILITY FOR MULTIPLE-SCLEROSIS IS DETERMINED, IN PART, BY INHERITANCE OF A 175-KB REGION OF THE TCR V-BETA-CHAIN LOCUS AND HLA CLASS-II GENES [J].
BEALL, SS ;
BIDDISON, WE ;
MCFARLIN, DE ;
MCFARLAND, HF ;
HOOD, LE .
JOURNAL OF NEUROIMMUNOLOGY, 1993, 45 (1-2) :53-60
[4]   THE GERMLINE REPERTOIRE OF T-CELL RECEPTOR BETA-CHAIN GENES IN PATIENTS WITH CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS [J].
BEALL, SS ;
CONCANNON, P ;
CHARMLEY, P ;
MCFARLAND, HF ;
GATTI, RA ;
HOOD, LE ;
MCFARLIN, DE ;
BIDDISON, WE .
JOURNAL OF NEUROIMMUNOLOGY, 1989, 21 (01) :59-66
[5]  
BENNUN A, 1991, P NATL ACAD SCI USA, V88, P2466, DOI 10.1073/pnas.88.6.2466
[6]   VACCINATION AGAINST AUTOIMMUNE ENCEPHALOMYELITIS WITH LYMPHOCYTE-T LINE CELLS REACTIVE AGAINST MYELIN BASIC-PROTEIN [J].
BENNUN, A ;
WEKERLE, H ;
COHEN, IR .
NATURE, 1981, 292 (5818) :60-61
[7]   IMMUNOHISTOLOGICAL ANALYSIS OF LYMPHOCYTE-T SUBSETS IN THE CENTRAL NERVOUS-SYSTEM IN CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS [J].
BOOSS, J ;
ESIRI, MM ;
TOURTELLOTTE, WW ;
MASON, DY .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1983, 62 (1-3) :219-232
[8]   MULTIPLE-SCLEROSIS SUSCEPTIBILITY - POPULATION AND TWIN STUDY OF POLYMORPHISMS IN THE T-CELL RECEPTOR BETA-GENE AND GAMMA-GENE REGION [J].
BRIANT, L ;
AVOUSTIN, P ;
CLAYTON, J ;
MCDERMOTT, M ;
CLANET, M ;
CAMBONTHOMSEN, A .
AUTOIMMUNITY, 1993, 15 (01) :67-73
[9]   BOTH RAT AND MOUSE T-CELL RECEPTORS SPECIFIC FOR THE ENCEPHALITOGENIC DETERMINANT OF MYELIN BASIC-PROTEIN USE SIMILAR V-ALPHA AND V-BETA CHAIN GENES EVEN THOUGH THE MAJOR HISTOCOMPATIBILITY COMPLEX AND ENCEPHALITOGENIC DETERMINANTS BEING RECOGNIZED ARE DIFFERENT [J].
BURNS, FR ;
LI, XO ;
SHEN, N ;
OFFNER, H ;
CHOU, YK ;
VANDENBARK, AA ;
HEBERKATZ, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (01) :27-39
[10]   FURTHER LOCALIZATION OF A MULTIPLE-SCLEROSIS SUSCEPTIBILITY GENE ON CHROMOSOME-7Q USING A NEW T-CELL RECEPTOR BETA-CHAIN DNA POLYMORPHISM [J].
CHARMLEY, P ;
BEALL, SS ;
CONCANNON, P ;
HOOD, L ;
GATTI, RA .
JOURNAL OF NEUROIMMUNOLOGY, 1991, 32 (03) :231-240