Diminished frequency of interleukin-10-secreting, T-cell receptor peptide-reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene

Authors

  • Arthur A. Vandenbark,

    Corresponding author
    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
    2. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
    3. Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon
    • R&D-31, P.O. Box 1034, VA Medical Center, Portland, OR 97207
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  • Tom Finn,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
    2. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
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  • David Barnes,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
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  • Nicole Culbertson,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
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  • Yuan K. Chou,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
    2. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
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  • Kevin Hicks,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
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  • Antony Bakke,

    1. Department of Pathology, Oregon Health Sciences University, Portland, Oregon
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  • Michele Mass,

    1. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
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  • Ruth Whitham,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
    2. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
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  • Halina Offner,

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
    2. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
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  • Dennis Bourdette

    1. Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, Oregon
    2. Department of Neurology, Oregon Health Sciences University, Portland, Oregon
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)-10-dependent bystander suppression. In this study, innate IL-10- and interferon (IFN)-γ-secreting T cells responsive to TCR peptides were quantified in peripheral blood mononuclear cells of MS patients and healthy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-γ frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10 frequency responses to the TCR peptides but normal responses to concanavalin A. Patients undergoing TCR-peptide vaccination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells was inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients have diminished frequencies of innate TCR-reactive T cells that may allow oligoclonal expansion of activated autoreactive Th1 effector cells expressing cognate V genes. J. Neurosci. Res. 66:171–176, 2001. Published 2001 Wiley-Liss, Inc.

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