Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis.
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.
Biegler
Brian W
BW
Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA.
Yan
Shirley X
SX
Ortega
Sterling B
SB
Tennakoon
Deepani K
DK
Racke
Michael K
MK
Karandikar
Nitin J
NJ
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
D016827:CD8 Antigens; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000068717:Glatiramer Acetate