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| Item Type: | Article |
|---|---|
| Title: | Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation |
| Creators Name: | Scholz, C., Patton, K.T., Anderson, D.E., 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 |
| ISSN: | 0022-1767 |
| Publisher: | American Association of Immunologists |
| Volume: | 160 |
| Number: | 3 |
| 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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