Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus.
Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus.
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DOI：
10.4049/jimmunol.160.5.2539
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发表时间：
1998-03
影响因子：
4.4
通讯作者：
K. Ohtsuka;J. Gray;M. M. Stimmler-M.;Bricia Toro;D. Horwitz
中科院分区：
文献类型：
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作者：
K. Ohtsuka;J. Gray;M. M. Stimmler-M.;Bricia Toro;D. Horwitz
TGF-β对免疫系统具有显著的抑制作用，但也作为具有下调活性的T细胞发育中的共刺激因子。这种细胞因子作为潜伏复合物分泌，并在细胞外转化为其活性形式。我们最近了解到，抗CD 2是淋巴细胞衍生的TGF-β的有效诱导剂，NK细胞是主要来源。本研究的目的是比较系统性红斑狼疮（SLE）患者与健康对照组血液淋巴细胞产生的组成性、抗CD 2诱导和精氨酸调节的TGF-β水平。使用一种高度敏感和特异性的生物测定法来评估TGF-β，我们报告了SLE患者未受刺激的PBL，特别是NK细胞亚群，产生活性TGF-β水平降低。抗CD 2抗体治疗后，SLE患者的活性TGF-β和总TGF-β浓度也降低。在了解到IL-2和TNF-α增强淋巴细胞产生活性TGF-β后，我们发现添加这些细胞因子不能将活性TGF-β增加到正常浓度。虽然我们观察到IL-10抑制活性TGF-β的产生，但这种细胞因子的拮抗作用无法完全纠正缺陷。在两个SLE患者的B细胞过度活跃，自发IgG的生产几乎被取消的TGF-β和IL-2的组合。因此，在SLE中这些细胞因子中的每一种的产生减少可能在B细胞过度活跃的持续中是重要的。
TGF-beta has marked inhibitory effects on the immune system but also serves as a costimulatory factor in the development of T cells with down-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source. The objective of this study was to compare levels of constitutive, anti-CD2-induced and cytokine-regulated TGF-beta produced by blood lymphocytes from patients with systemic lupus erythematosus (SLE) in comparison with healthy controls. Using a highly sensitive and specific bioassay to assess TGF-beta, we report that unstimulated PBL from SLE patients, especially the NK cell subset, produced decreased levels of active TGF-beta. In response to anti-CD2, concentrations of active and total TGF-beta were also decreased in SLE. After learning that IL-2 and TNF-alpha enhance lymphocyte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrations. Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity.