Multiple sclerosis immunology The healthy immune system vs the MS immune system

被引:129
作者
Kasper, Lloyd H. [1 ,2 ,3 ]
Shoemaker, Jennifer
机构
[1] Dartmouth Med Sch, Dartmouth Hitchcock Multiple Sclerosis Clin, Dept Neurol, Lebanon, NH 03756 USA
[2] Dartmouth Med Sch, Dartmouth Hitchcock Multiple Sclerosis Clin, Dept Med, Lebanon, NH 03756 USA
[3] Dartmouth Med Sch, Dartmouth Hitchcock Multiple Sclerosis Clin, Dept Microbiol Immunol, Lebanon, NH 03756 USA
关键词
REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; DENDRITIC CELLS; PHASE-II; DOUBLE-BLIND; TH17; CELLS; OPEN-LABEL; B-CELLS; OSTEOPONTIN;
D O I
10.1212/WNL.0b013e3181c97c8f
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by both inflammation and axonal degeneration. The resulting demyelination and subsequent degeneration of axons account for the disability of patients with MS. Early investigations indicated that disease progression was driven by CD4(+) effector T cells. However, clinical therapies specifically targeting these cells have, for the most part, not been effective. Therefore, new areas of research in experimental autoimmune encephalomyelitis (the experimental model of MS) and human MS have identified previously unknown contributions to disease pathogenesis, including interleukin-17-producing T helper 17 cells, B cells, CD8(+) T cells, and both CD4(+) and CD8(+) T-regulatory cells. Research into the respective mechanisms of action of these cells has identified novel therapeutic targets to combat this devastating disease. This article reviews the autoimmune response in patients with MS compared with individuals without MS and summarizes the fundamental differences in the immunologic response between people with and without MS. Investigations into these autoimmune differences and the disruption of the homeostatic balance of the immune system will help guide future research into MS therapeutics, with particular attention to the long-term management of this disease. NEUROLOGY 2010;74(Suppl1):S2-S8
引用
收藏
页码:S2 / S8
页数:7
相关论文
共 54 条
[11]   Interferon beta-1a therapy enhances CD4+ regulatory T-cell function:: An ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis [J].
de Andres, Clara ;
Aristimuno, Carol ;
de las Heras, Virginia ;
Martinez-Gines, M. Luisa ;
Bartolome, Manuel ;
Arroyo, Rafael ;
Navarro, Joaquin ;
Gimenez-Roldan, Santiago ;
Fernandez-Cruz, Eduardo ;
Sanchez-Ramon, Silvia .
JOURNAL OF NEUROIMMUNOLOGY, 2007, 182 (1-2) :204-211
[12]   Depending on their maturation state, splenic dendritic cells induce the differentiation of CD4+ T lymphocytes into memory and/or effector cells in vivo [J].
de Heusch, M ;
Oldenhove, G ;
Urbain, J ;
Thielemans, K ;
Maliszewski, C ;
Leo, O ;
Moser, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (07) :1861-1869
[13]   An APRIL to remember: novel TNF ligands as therapeutic targets [J].
Dillon, SR ;
Gross, JA ;
Ansell, SM ;
Novak, AJ .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (03) :235-246
[14]   T-Helper 17 Cells Expand in Multiple Sclerosis and Are Inhibited by Interferon-β [J].
Durelli, Luca ;
Conti, Laura ;
Clerico, Marinella ;
Boselli, Daniela ;
Contessa, Giulia ;
Ripellino, Paolo ;
Ferrero, Bruno ;
Eid, Pierre ;
Novelli, Francesco .
ANNALS OF NEUROLOGY, 2009, 65 (05) :499-509
[15]   Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction [J].
Fitzgerald, KA ;
Palsson-McDermott, EM ;
Bowie, AG ;
Jefferies, CA ;
Mansell, AS ;
Brady, G ;
Brint, E ;
Dunne, A ;
Gray, P ;
Harte, MT ;
McMurray, D ;
Smith, DE ;
Sims, JE ;
Bird, TA ;
O'Neill, LAJ .
NATURE, 2001, 413 (6851) :78-83
[16]   FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis [J].
Fujii, R. ;
Kanai, T. ;
Nemoto, Y. ;
Makita, S. ;
Oshima, S. ;
Okamoto, R. ;
Tsuchiya, K. ;
Totsuka, T. ;
Watanabe, M. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2006, 291 (02) :G267-G274
[17]   The type IIFN induction pathway constrains Th17-mediated autoimmune inflammation in mice [J].
Guo, Beichu ;
Chang, Elmer Y. ;
Cheng, Genhong .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (05) :1680-1690
[18]   Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis [J].
Haas, J ;
Hug, A ;
Viehöver, A ;
Fritzsching, B ;
Falk, CS ;
Filser, A ;
Vetter, T ;
Milkova, L ;
Korporal, M ;
Fritz, B ;
Storch-Hagenlocher, B ;
Krammer, PH ;
Suri-Payer, E ;
Wildemann, B .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (11) :3343-3352
[19]   Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions [J].
Hatterer, Eric ;
Touret, Monique ;
Belin, Marie-Francoise ;
Honnorat, Jerome ;
Nataf, Serge .
PLOS ONE, 2008, 3 (10)
[20]   B-cell depletion with Rituximab in relapsing-remitting multiple sclerosis [J].
Hauser, Stephen L. ;
Waubant, Emmanuelle ;
Arnold, Douglas L. ;
Vollmer, Timothy ;
Antel, Jack ;
Fox, Robert J. ;
Bar-Or, Amit ;
Panzara, Michael ;
Sarkar, Neena ;
Agarwal, Sunil ;
Langer-Gould, Annette ;
Smith, Craig H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (07) :676-688