Tumor necrosis factor-α blockade leads to decreased peripheral T cell reactivity and increased dendritic cell number in peripheral blood of patients with ankylosing spondylitis

Abstract

Objective. To study the effect of tumor necrosis factor-α (TNF-α) antagonist (etanercept) treatment on the peripheral T cell reactivity of patients with ankylosing spondylitis (AS). Methods. Peripheral blood mononuclear cells were collected from 40 patients with AS at baseline, after 2 and 6 weeks of etanercept treatment or placebo treatment, and from healthy controls. The number of cells secreting various cytokines was detected by enzyme linked immunospot. Serum soluble interleukin 2 (IL-2) receptor level was measured by ELISA. T cell proliferation was assayed with the WST-1 live cell-staining method. The myeloid dendritic cell (mDC) and regulatory T cell (Treg) levels were analyzed by fluorescence activated cell sorting. Results. After 2 and 6 weeks of etanercept treatment, the number of TNF-α-secreting monocytes decreased. Although the T cell proliferation rate remained stable, the number of T cells secreting IL-2 and interferon-γ under anti-CD3/anti-CD28 stimulation was significantly decreased. The level of serum soluble IL-2R (sIL-2R), a T cell activation marker, also declined. The changes in T cell reactivity were correlated with a significant increase in MHC Class II-positive mDC cells in circulation. An increase in Treg cell numbers was also observed. Conclusion. The anti-TNF-α therapy blockaded MHC Class II-positive mDC maturation, enhanced regulatory T cell levels, and suppressed the functions of effector T cells. The reduced T cell reactivity could contribute to the efficacy of the TNF-α antagonist therapy in patients with AS. The Journal of Rheumatology Copyright © 2008. All rights reserved.