The effect of blockade of tumor necrosis factor α on VLA-1+T-cells in rheumatoid arthritis patients

Ilan Bank, Shomron Ben-Horin, Itamar Goldstein, Alexander Koltakov, Pnina Langevitz, Michael Ehrenfeld, Esther Rosenthal, Hanan Gur

Research output: Contribution to journalArticlepeer-review

Abstract

The α1β1 integrin, very late antigen (VLA)-1, characterizes collagen adherent interferon (IFN) γ producing memory T cells in inflamed synovium. We now report that the mean percentage of VLA-1+ T cells is significantly lower among peripheral blood mononuclear cells of rheumatoid patients responsive to antitumor necrosis factor (TNF) α therapy than of those with active disease not receiving therapy. Neutralization of TNFα during in vitro polyclonal activation of VLA-1- T cells reduced differentiation to expression of VLA-1 and inhibited secretion of IFNγ, but did not affect integrin expression on in vivo differentiated VLA-1+ T cells. Moreover, synovial fluids of patients relapsing during and after therapy were enriched in VLA-1+ T cells and lines derived from VLA-1+ T cells in peripheral blood of treated patients retained collagen binding and secreted IFN γ. Thus, whereas therapy decreases VLA-1+ T cells in rheumatoid arthritis patients, a subset is resistant and contributes to residual and recurring inflammation.

Original languageEnglish
Pages (from-to)580-588
Number of pages9
JournalJournal of Clinical Immunology
Volume27
Issue number6
DOIs
StatePublished - Nov 2007

Keywords

  • Arthritis
  • CD45RO
  • Collagen type IV
  • Integrins
  • Memory T cells
  • T cells
  • VLA-1

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