title: Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis.
abstract: T cell responses to myelin basic protein (MBP) may play an important role in the pathogenesis of multiple sclerosis (MS). If MBP-reactive T cells are involved in the disease processes and undergo clonal activation and expansion, their precursor frequency would be increased in patients with MS. The frequency of MBP-reactive T cells is also influenced by regulatory mechanisms in vivo, including apoptotic deletion. In this study, we examined changes in the frequency of MBP-reactive T cells in patients with MS as a function of the apoptotic deletional mechanism in vivo, using a cell culture-based assay. A significantly increased frequency of MBP-reactive T cells was found in patients with MS relative to healthy individuals only when Fas-ligand antibody was used to block apoptosis. This result indicates that a significant proportion of MBP-reactive T cells are sensitive to apoptosis and are not deleted in vivo in patients with MS, as opposed to healthy individuals, thus suggesting a functional deficit in apoptotic deletional mechanism. Surviving Fas-sensitive MBP-reactive T cell lines represent distinct subpopulations preferentially recognizing the 111-139 region of MBP and exhibiting a Th2 cytokine profile. The findings are relevant to our understanding of regulation of MBP-reactive T cells in vivo in MS.
authors.affiliation: Department of Neurology, Baylor College of Medicine, and Baylor-Methodist Multiple Sclerosis Center, Houston 77030, USA. jzang@bcm.tmc.edu
authors.forename: Y C
authors.initials: YC
authors.lastname: Zang
authors.forename: M M
authors.initials: MM
authors.lastname: Kozovska
authors.forename: J
authors.initials: J
authors.lastname: Hong
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Mann
authors.forename: J M
authors.initials: JM
authors.lastname: Killian
authors.forename: V M
authors.initials: VM
authors.lastname: Rivera
authors.forename: J Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D019014:fas Receptor