The Effect of Blockade of Tumor Necrosis Factor α on VLA-1+T-Cells in Rheumatoid Arthritis Patients
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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.
KeywordsT cells VLA-1 integrins collagen type IV CD45RO memory T cells arthritis
This work was supported in part by an investigator initiated non restricted grant from Biogen Idec to I. B.
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