title: Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation.
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.
authors.affiliation: Laboratory of Molecular Immunology, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Scholz
authors.forename: K T
authors.initials: KT
authors.lastname: Patton
authors.forename: D E
authors.initials: DE
authors.lastname: Anderson
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
mesh_terms: D000069594:Abatacept; D015703:Antigens, CD / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000494:pharmacology; D001324:Autoantigens / Q000276:immunology*; D018122:B7-1 Antigen / Q000494:pharmacology*; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology; D013936:Thymidine / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018984:Epitopes, T-Lymphocyte; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; D015847:Interleukin-4; D000069594:Abatacept; D013936:Thymidine