文章基本信息

标题：Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand
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作者：Konstantin E. Balashov ; Derek R. Smith ; Samia J. Khoury 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1997
卷号：94
期号：2
页码：599-603
DOI：10.1073/pnas.94.2.599
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be a cell-mediated autoimmune disease in which interferon {gamma} (IFN-{gamma}) plays an important role. There is increased IFN-{gamma} secretion in MS, and IFN-{gamma} administration induces exacerbations of disease. We found that interleukin 12 (IL-12) was responsible for raised IFN-{gamma} secretion in MS as anti-IL-12 antibodies reversed raised anti-CD3-induced IFN-{gamma} in MS patients to normal levels. Furthermore, we found a marked increase in T cell receptor-mediated IL-12 secretion in progressive MS patients vs. controls (24.8 {+/-} 7.7 pg/ml vs. 1.5 {+/-} 1.0 pg/ml, P = 0.003) and vs. relapsing-remitting patients (3.7 {+/-} 1.4 pg/ml, P < 0.05). Investigation of the cellular basis for raised IL-12 demonstrated that T cells from MS patients induced IL-12 secretion from non-T cells, and that T cells from MS patients could even drive non-T cells from normal subjects to produce increased IL-12. Anti-CD40 ligand antibody completely blocked IL-12 secretion induced by activated T cells, and we found increased CD40 ligand expression by activated CD4+ T cells in MS patients vs. controls. The CD40 ligand-dependent Th1-type immune activation was observed in the progressive but not in the relapsing-remitting form of MS, suggesting a link to disease pathogenesis and progression and providing a basis for immune intervention in the disease.
关键词：autoimmunity ; gp39 ; interferon-γ