Pang Liping, Wang Lisha, Suo Talin, Hao Huiqin, Fang Xianfeng, Jia Junying, Huang Feng, Tang Jie
National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, China.
J Rheumatol. 2008 Nov;35(11):2220-8. doi: 10.3899/jrheum.080219.
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).
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.
. 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.
. 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.
研究肿瘤坏死因子-α（TNF-α）拮抗剂（依那西普）治疗对强直性脊柱炎（AS）患者外周血T细胞反应性的影响。
收集40例AS患者在基线时、依那西普治疗或安慰剂治疗2周和6周后的外周血单个核细胞，以及健康对照者的外周血单个核细胞。采用酶联免疫斑点法检测分泌各种细胞因子的细胞数量。用酶联免疫吸附测定法检测血清可溶性白细胞介素2（IL-2）受体水平。采用WST-1活细胞染色法检测T细胞增殖。通过荧光激活细胞分选分析髓样树突状细胞（mDC）和调节性T细胞（Treg）水平。
依那西普治疗2周和6周后，分泌TNF-α的单核细胞数量减少。尽管T细胞增殖率保持稳定，但在抗CD3/抗CD28刺激下分泌IL-2和干扰素-γ的T细胞数量显著减少。T细胞活化标志物血清可溶性IL-2R（sIL-2R）水平也下降。T细胞反应性的变化与循环中MHC II类阳性mDC细胞显著增加相关。还观察到Treg细胞数量增加。
抗TNF-α治疗阻断了MHC II类阳性mDC的成熟，提高了调节性T细胞水平，并抑制了效应T细胞的功能。T细胞反应性降低可能有助于TNF-α拮抗剂治疗AS患者的疗效。
