OBJECTIVE: To study the effect of tumor necrosis factor-alpha (TNF-alpha) 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 ofetanercept treatment or placebo treatment, and from healthy controls. The number of cells secreting various cytokines was detected by enzyme linked immunospot. Serum soluble interleukin2 (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-alpha-secreting monocytes decreased. Although the T cell proliferation rate remained stable, the number of T cells secreting IL-2 and interferon-gamma 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-alpha 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-alpha antagonist therapy in patients with AS.
RCT Entities:
OBJECTIVE: To study the effect of tumor necrosis factor-alpha (TNF-alpha) 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-alpha-secreting monocytes decreased. Although the T cell proliferation rate remained stable, the number of T cells secreting IL-2 and interferon-gamma 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-alpha 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-alpha antagonist therapy in patients with AS.
Authors: Bhavana Priyadharshini; Raymond M Welsh; Dale L Greiner; Rachel M Gerstein; Michael A Brehm Journal: PLoS One Date: 2010-11-24 Impact factor: 3.240