Abstract
Patients with multiple sclerosis (MS) show a high prevalence of myelin-reactive CD8+ and CD4+ T-cell responses, which are the putative effectors/modulators of CNS neuropathology. Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal compositions of neuroantigen-targeting T-cells from RRMS patients and controls. CDR3 region analysis of TCRβ chains revealed biased use of specific TCRBV-bearing CD4+ clones. CD8+ clones showed homology to published TCR from CNS-infiltrating T-cells in MS lesions. These studies are the first description of TCR usage of CNS-specific CD8+ T-cells and provide insights into their potential regulatory role in disease.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication types
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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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Antibodies / metabolism
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / pathology
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Cloning, Molecular
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Female
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Flow Cytometry / methods
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Humans
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Male
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Middle Aged
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Molecular Sequence Data
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Multiple Sclerosis / cerebrospinal fluid
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Multiple Sclerosis / pathology*
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Myelin Basic Protein / genetics
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Myelin Basic Protein / metabolism*
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Myelin Proteolipid Protein / genetics
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Myelin Proteolipid Protein / metabolism*
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Myelin Sheath / immunology
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Receptors, Antigen, T-Cell
Substances
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Antibodies
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Myelin Basic Protein
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Myelin Proteolipid Protein
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Receptors, Antigen, T-Cell