The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis

被引:187
作者
Hohlfeld, R
Kerschensteiner, M
Stadelmann, C
Lassmann, H
Wekerle, H
机构
[1] Univ Munich, Klinikum Grosshadern, Inst Clin Neuroimmunol, D-81366 Munich, Germany
[2] Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81366 Munich, Germany
[3] Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany
[4] Univ Vienna, Inst Neurol, A-1090 Vienna, Austria
关键词
autoimmunity; immunotherapy; multiple sclerosis; neuroprotection; neurotrophic factors;
D O I
10.1016/S0165-5728(00)00233-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Autoreactive T cells ale a component of the normal immune system. It has been proposed that some of these autoreactive T cells even have a protective function. Recent studies support this notion by demonstrating that (a) myelin basic-protein (MBP-) specific T cells show neuroprotective effects in vivo, and (b) activated antigen-specific human T cells and other immune cells produce bioactive brain-derived neurotrophic factor (BDNF) in vitro. Furthermore, BDNF is expressed in different types of inflammatory cells in brain lesions of patients with acute disseminated leukoencephalopathy or multiple sclerosis. We postulate that the neuroprotective effect of T cells and other immune cells observed in vivo is at least partially mediated by BDNF and other neurotrophic factors. The concept of neuroprotective autoimmunity has obvious implications for the therapy of multiple sclerosis and other neuroimmunological diseases. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:161 / 166
页数:6
相关论文
共 42 条
[1]  
Batchelor PE, 1999, J NEUROSCI, V19, P1708
[2]  
Besser M, 1999, J IMMUNOL, V162, P6303
[3]   THE COGNITIVE PARADIGM AND THE IMMUNOLOGICAL HOMUNCULUS [J].
COHEN, IR .
IMMUNOLOGY TODAY, 1992, 13 (12) :490-494
[4]   FUTURE-PROSPECTS FOR THE MANAGEMENT OF MULTIPLE-SCLEROSIS [J].
COMPSTON, A .
ANNALS OF NEUROLOGY, 1994, 36 :S146-S150
[5]   EXPRESSION OF NERVE GROWTH-FACTOR AND NERVE GROWTH-FACTOR RECEPTOR TYROSINE KINASE TRK IN ACTIVATED CD4-POSITIVE T-CELL CLONES [J].
EHRHARD, PB ;
ERB, P ;
GRAUMANN, U ;
OTTEN, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) :10984-10988
[6]   Axonal damage in acute multiple sclerosis lesions [J].
Ferguson, B ;
Matyszak, MK ;
Esiri, MM ;
Perry, VH .
BRAIN, 1997, 120 :393-399
[7]   Gene transfer into CD4+ T lymphocytes:: Green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses [J].
Flügel, A ;
Willem, M ;
Berkowicz, T ;
Wekerle, H .
NATURE MEDICINE, 1999, 5 (07) :843-847
[8]   Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons [J].
Gravel, C ;
Gotz, R ;
Lorrain, A ;
Sendtner, M .
NATURE MEDICINE, 1997, 3 (07) :765-770
[9]   Accumulation of passively transferred primed T cells independently of their antigen specificity following central nervous system trauma [J].
Hirschberg, DL ;
Moalem, G ;
He, J ;
Mor, F ;
Cohen, IR ;
Schwartz, M .
JOURNAL OF NEUROIMMUNOLOGY, 1998, 89 (1-2) :88-96
[10]   REGIONAL DISTRIBUTION OF BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER-RNA IN THE ADULT-MOUSE BRAIN [J].
HOFER, M ;
PAGLIUSI, SR ;
HOHN, A ;
LEIBROCK, J ;
BARDE, YA .
EMBO JOURNAL, 1990, 9 (08) :2459-2464