Cytokine producing CD8+ T cells are correlated to MRI features of tissue destruction in MS

被引:27
作者
Killestein, J
Eikelenboom, MJ
Izeboud, T
Kalkers, NF
Adèr, HJ
Barkhof, F
Van Lier, RAW
Uitdehaag, BMJ
Polman, CH
机构
[1] VU Med Ctr, Dept Neurol, Amsterdam, Netherlands
[2] CLB, Dept Clin Viroimmunol, Amsterdam, Netherlands
[3] VU Med Ctr, MS MRI Ctr, Amsterdam, Netherlands
[4] VU Med Ctr, Dept Clin Epidemiol & Biostat, Amsterdam, Netherlands
[5] AMC, Dept Expt Immunol, Amsterdam, Netherlands
关键词
cytokines; multiple sclerosis; CD8(+) T cells; MRI; EDSS;
D O I
10.1016/S0165-5728(03)00265-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Specific T-cell subsets and their ability to produce cytokines have been involved in concepts of multiple sclerosis (MS) pathogenesis. Evidence to link cytokine producing T-cell subsets to magnetic resonance imaging (MRI) features of tissue destruction, however, is limited. Cytokine flow cytometry was performed in 124 patients with different subtypes of MS. In a subgroup of 69 patients, from whom longitudinal MRI was available, the ability of circulating types I and 2 helper T cells to produce cytokines was correlated to changes in T1 hypointense and T2 hyperintense lesion load (LL) on brain MRI during 3 years of follow-up. Significant negative correlations were found between baseline CD8(+) T-cell subsets producing IL-2, IL-4 or IL-13 and the change in T1 LL. Subgroup analyses demonstrated that in RRMS, CD8(+) T cells producing IL-2, IL-4 or IL-13, and in PPMS, CD8(+) IL-10(+) T cells correlated negatively with T1 LL. To our knowledge, this study provides the first direct immumophenotypic evidence of cytokine producing CD8+ T cells being directly related to long-term development of MRI features of demyelination and axonal loss. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:141 / 148
页数:8
相关论文
共 39 条
[11]   A pathogenic role for myelin-specific CD8+ T cells in a model for multiple sclerosis [J].
Huseby, ES ;
Liggitt, D ;
Brabb, T ;
Schnabel, B ;
Öhlén, C ;
Goverman, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (05) :669-676
[12]   Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients [J].
Jacobsen, M ;
Cepok, S ;
Quak, E ;
Happel, M ;
Gaber, R ;
Ziegler, A ;
Schock, S ;
Oertel, WH ;
Sommer, N ;
Hemmer, B .
BRAIN, 2002, 125 :538-550
[13]  
Jurewicz A, 1998, J IMMUNOL, V160, P3056
[14]   Optimizing the association between disability and biological markers in MS [J].
Kalkers, NF ;
Bergers, E ;
Castelijns, JA ;
van Walderveen, MAA ;
Bot, JCJ ;
Adèr, HJ ;
Polman, CH ;
Barkhof, F .
NEUROLOGY, 2001, 57 (07) :1253-1258
[15]   Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis [J].
Karandikar, NJ ;
Crawford, MP ;
Yan, X ;
Ratts, RB ;
Brenchley, JM ;
Ambrozak, DR ;
Lovett-Racke, AE ;
Frohman, EM ;
Stastny, P ;
Douek, DC ;
Koup, DA ;
Racke, MK .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (05) :641-649
[16]   Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation? [J].
Kerschensteiner, M ;
Gallmeier, E ;
Behrens, L ;
Leal, VV ;
Misgeld, T ;
Klinkert, WEF ;
Kolbeck, R ;
Hoppe, E ;
Oropeza-Wekerle, RL ;
Bartke, I ;
Stadelmann, C ;
Lassmann, H ;
Wekerle, H ;
Hohlfeld, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (05) :865-870
[17]   Active MRI lesion appearance in MS patients is preceded by fluctuations in circulating T-helper 1 and 2 cells [J].
Killestein, J ;
Rep, MHG ;
Barkhof, F ;
Roos, MTL ;
Adèr, HJ ;
van Lier, RAW ;
Polman, CH .
JOURNAL OF NEUROIMMUNOLOGY, 2001, 118 (02) :286-294
[18]   Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease [J].
Killestein, J ;
Den Drijver, BF ;
Van der Graaff, WL ;
Uitdehaag, BMJ ;
Polman, CH ;
Van Lier, RAW .
MULTIPLE SCLEROSIS, 2001, 7 (03) :145-150
[19]   TNFα production by CD4+ T cells predicts long-term increase in lesion load on MRI in MS [J].
Killestein, J ;
Kalkers, NF ;
Meilof, JF ;
Barkhof, F ;
van Lier, RAW ;
Polman, CH .
NEUROLOGY, 2001, 57 (06) :1129-1131
[20]   LESS MORTALITY BUT MORE RELAPSES IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN CD8-/- MICE [J].
KOH, DR ;
FUNGLEUNG, WP ;
HO, A ;
GRAY, D ;
ACHAORBEA, H ;
MAK, TW .
SCIENCE, 1992, 256 (5060) :1210-1213