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Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation

Item Type:Article
Title:Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation
Creators Name:Scholz, C. and Patton, K.T. and Anderson, D.E. and Freeman, G.J. and Hafler, D.A.
Abstract:Multiple sclerosis (MS) is an inflammatory disease of the myelinated central nervous system that is postulated to be induced by myelin-reactive CD4 T cells. T cell activation requires an antigen-specific signal through the TCR and a costimulatory signal, which can be mediated by B7-1 or B7-2 engagement of CD28. To directly examine the activation state of myelin-reactive T cells in MS, the costimulation requirements necessary to activate myelin basic protein (MBP) or tetanus toxoid (TT)-reactive CD4 T cells were compared between normal controls and MS patients. Peripheral blood T cells were stimulated with Chinese hamster ovary (CHO) cells transfected either with DRB1*1501/DRA0101 chains (t-DR2) alone, or in combination with, B7-1 or B7-2. In the absence of costimulation, T cells from normal subjects stimulated with the recall antigen TT p830-843 were induced to expand and proliferate, but stimulation with MBP p85-99 did not have this effect. In marked contrast, T cells from patients with MS stimulated with MBP p85-99 in the absence of B7-1 or B7-2 signals expanded and proliferated. Thus, MBP-reactive CD4 T cells in patients with MS are costimulation independent and have been previously activated in vivo. These experiments provide further direct evidence for a role of activated MBP-specific CD4 T cells in the pathogenesis of MS.
Keywords:Autoantigens, CD80 Antigens, CD86 Antigens, Clone Cells, Differentiation Antigens, Immunoconjugates, Immunoglobulin Fc Fragments, Immunosuppressive Agents, Interleukin-4, Lymphocyte Activation, Membrane Glycoproteins, Multiple Sclerosis, Myelin Basic Proteins, Recombinant Fusion Proteins, T-Lymphocyte Epitopes, T-Lymphocyte Subsets, Tetanus Toxoid, Thymidine
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:1532-1538
Date:1 February 1998
Official Publication:http://www.jimmunol.org/cgi/content/abstract/160/3/1532
PubMed:View item in PubMed

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