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.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD8 Antigens / drug effects
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CD8 Antigens / genetics
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CD8 Antigens / immunology
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CD8-Positive T-Lymphocytes / drug effects*
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CD8-Positive T-Lymphocytes / immunology*
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Clone Cells / drug effects
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Clone Cells / immunology
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Female
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Flow Cytometry / methods
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Glatiramer Acetate
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Humans
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Immunologic Factors / pharmacology
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Immunologic Factors / therapeutic use
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Immunosuppressive Agents / pharmacology
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Immunosuppressive Agents / therapeutic use
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Male
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Middle Aged
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Molecular Sequence Data
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / immunology*
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Multiple Sclerosis / physiopathology
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Peptides / pharmacology*
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Peptides / therapeutic use
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Polymerase Chain Reaction / methods
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Receptors, Antigen, T-Cell, alpha-beta / drug effects
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
Substances
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CD8 Antigens
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Immunologic Factors
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Immunosuppressive Agents
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Peptides
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Receptors, Antigen, T-Cell, alpha-beta
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Glatiramer Acetate