Correlation of T and B cell activities in vitro and serum IL-2 levels in systemic lupus erythematosus.

Correlation of T and B cell activities in vitro and serum IL-2 levels in systemic lupus erythematosus.
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DOI:
10.4049/jimmunol.141.3.827
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发表时间:
1988-08
影响因子:
4.4
通讯作者:
Y. P. Huang;L. Perrin;P. Miescher;R. Zubler
Y. P. Huang;L. Perrin;P. Miescher;R. Zubler
中科院分区:
医学2区
文献类型:
--
作者:
Y. P. Huang;L. Perrin;P. Miescher;R. Zubler

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只有少数研究表明,SLE中B细胞的过度活跃可能依赖于Th细胞的激活。特别是循环中的CD4+细胞表达Ia。我们以前的研究表明,SLE患者CD4+细胞体外分泌IL-2的能力下降,在培养几天后恢复正常。这表明循环中存在激活的、耗尽的T细胞。在这项研究中,我们报告了几个关于SLE T细胞功能的观察。1)外周血淋巴细胞体外IL-2分泌减少与其自发免疫球蛋白分泌增加显著相关,22例患者接受激素加环孢素A免疫抑制治疗后,上述两种异常均得到很大程度的纠正。2)18例活动期(体外IL-2分泌水平低)患者中,9例血清IL-2水平升高,其中2例血清中含有IL-2生物学活性,1例血清层析显示IL-2为可与6M尿素解离的大分子复合体(MR约50000)。血清IL-2R水平也经常升高,即使在活动度较低的SLE中也是如此。3)在细胞培养实验中,9例活动期SLE患者中有6例患者的B细胞经自体T细胞单独作用(3例)或与rIL-2协同作用(3例)后,B细胞的免疫球蛋白G分泌增加,与供者B细胞相比,所有9例患者的B细胞均表现出较高的IL-2反应性。综上所述,这些结果提供了新的证据,表明T细胞激活增加在SLE中发生并发挥作用。
There have been only a few studies indicating that B cell hyperactivity in SLE could depend on Th cell activation. In particular, circulating CD4+ cells were found to express Ia. Our own previous investigations have shown that the decreased IL-2 secretion capacity in vitro of CD4+ cells in SLE is restored to normal when the cells are rested for a few days in culture. This suggested the presence of activated, exhausted T cells in the circulation. In this study, we report several observations concerning T cell function in SLE. 1) Decreased IL-2 secretion in vitro of PBL was found to correlate significantly with increased spontaneous IgG secretion of such cells; immunosuppressive treatment of 22 patients with steroids plus cyclosporin A led, to a large extent, to a correction of both abnormalities. 2) 9 of 18 patients with active disease (and low IL-2 secretion in vitro) had increased IL-2 levels in serum by ELISA; two sera contained IL-2 biologic activity, and chromatography of one serum showed IL-2 in a high molecular size complex (Mr approximately 50,000) dissociable with 6 M urea. The serum levels of IL-2R were also frequently increased, even in less active SLE. 3) In cell culture experiments, the IgG secretion by purified B cells from 6 of 9 patients with active SLE was increased by autologous T cells acting either alone (3 patients) or synergistically with rIL-2 (3 patients); the B cells from all 9 patients showed increased IL-2 responsiveness compared with blood donor B cells. Taken together, these results provide new evidence that increased T cell activation occurs and plays a role in SLE.