title: Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis.
abstract: We have demonstrated that GA therapy induces a differential upregulation of GA-specific, cytotoxic/suppressor CD8+ T-cell responses in MS patients. We utilized a novel combination of flow sorting and anchored PCR to analyze the evolving clonal composition of GA-specific CD4+ and CD8+ T-cells. TCRbeta chain analysis revealed the development of an oligoclonal GA-specific CD8+ repertoire with persistence of dominant clones over long periods. Interestingly, some sequences resembled published oligoclonal CD8+ TCR sequences from MS lesions. In contrast, GA-specific CD4+ responses were polyclonal and showed continual evolution of their repertoire. This clonotypic and functional analysis provides mechanistic insights into GA therapy.
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Biegler
authors.forename: Shirley X
authors.initials: SX
authors.lastname: Yan
authors.forename: Sterling B
authors.initials: SB
authors.lastname: Ortega
authors.forename: Deepani K
authors.initials: DK
authors.lastname: Tennakoon
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.forename: Nitin J
authors.initials: NJ
authors.lastname: Karandikar
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000068717:Glatiramer Acetate