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.
Key Indexing Terms:Footnotes
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L. Pang, PhD; T. Suo, MS; X. Fang, MS; J. Jia, BS; J. Tang, PhD, National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences; L. Wang, MD; H. Hao, MD; F. Huang, MD, Department of Rheumatology, Chinese PLA General Hospital.
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Drs. Pang and Wang contributed equally to this report.
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Supported in part by National Natural Science Foundation of China grant A30571726.
- Accepted for publication July 3, 2008.