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

Arthur A. Vandenbark, Tom Finn, David Barnes, Nicole Culbertson, Yuan K. Chou, Kevin Hicks, Antony Bakke, Michele Mass, Ruth Whitham, Halina Offner, Dennis Bourdette

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)171-176
Number of pages6
JournalJournal of Neuroscience Research
Volume66
Issue number2
DOIs
StatePublished - Oct 15 2001
Externally publishedYes

Keywords

  • Immunoregulation
  • Multiple sclerosis
  • T cells
  • T-cell receptor peptides

ASJC Scopus subject areas

  • Neuroscience(all)

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