Migita K, Eguchi K, Kawabe Y, Nakamura T, Shirabe S, Tsukada T, Ichinose Y, Nakamura H, Nagataki S
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Transplantation. 1997 Feb 27;63(4):583-7. doi: 10.1097/00007890-199702270-00017.
High-dose steroid pulse therapy is effective in transplant rejection and severe autoimmune diseases. Our goal was to identify the mechanism by which high-dose steroid exerts specific immunosuppressive actions. In this study, we investigated the in vivo effects of high-dose (1 g) methylprednisolone infusion on peripheral blood T lymphocyte apoptosis induction in 15 patients with severe autoimmune diseases. DNA fragmentation was detected in peripheral blood T cells isolated from these patients after 2 and 4 hr of steroid infusion. In contrast, T cells isolated from the same patients before or 8 or more hours after infusion did not show DNA fragmentation. DNA fragmentation was more significant in CD4+ than CD8+ T cells. The susceptibility of CD4+ T cells to apoptosis was associated with a lower expression of Bcl-2 in these cells compared with that on CD8+ T cells. To support the T-cell apoptosis induction by pulse therapy, peripheral blood T cells from normal subjects underwent DNA fragmentation after in vitro exposure to 2.5-10 microg/ml of methylprednisolone for 30 min. Our results indicate that induction of peripheral blood T-cell apoptosis is an important mechanism contributing to the immunosuppression observed after high-dose steroid therapy.
大剂量类固醇冲击疗法对移植排斥反应和严重自身免疫性疾病有效。我们的目标是确定大剂量类固醇发挥特异性免疫抑制作用的机制。在本研究中，我们调查了大剂量（1克）甲泼尼龙静脉输注对15例严重自身免疫性疾病患者外周血T淋巴细胞凋亡诱导的体内效应。在类固醇输注2小时和4小时后，从这些患者分离的外周血T细胞中检测到DNA片段化。相比之下，在输注前或输注8小时及更长时间后从同一患者分离的T细胞未显示DNA片段化。CD4⁺ T细胞中的DNA片段化比CD8⁺ T细胞更显著。与CD8⁺ T细胞相比，CD4⁺ T细胞对凋亡的易感性与这些细胞中Bcl-2表达较低有关。为了支持冲击疗法诱导T细胞凋亡，正常受试者的外周血T细胞在体外暴露于2.5 - 10微克/毫升甲泼尼龙30分钟后发生了DNA片段化。我们的结果表明，外周血T细胞凋亡的诱导是大剂量类固醇治疗后观察到的免疫抑制的重要机制。
