Fas ligands peripheral lymphocytes from patients with systemic lupus erythematosus

系统性红斑狼疮患者的 Fas 配体外周淋巴细胞

• 批准号: 09670497
• 负责人: TAKENO Mitsuhiro
• 金额: $ 1.92万
• 依托单位: St.Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670497/
• 关键词: systemic lupus erythematosus; Fas ligand; apoptosis; anti-Fas ligand autoantibody; autoreactive lymphocytes; Fasリガンド; 抗Fasリンガンド自己抗体

Fas-Fas ligand (FasL) interaction maintains immunological tolerance by apoptosis of autoreactive lymphocytes. Indeed, mice with mutations in Fas or Fas ligand develop lupus-like autoimmune disease. We here examined the expression of Fas ligands on peripheral blood lymphocytes (PBL) from patients with systemic lupus erythematosus (SLE) by RT-PCR and immunoblotting techniques. We found that PBL constitutively expressed Fas ligands in most of SLE patients, whereas PBL from normal donors never expressed Fas ligands unless they were stimulated in vitro. Flowcytometric analysis demonstrated Fas ligand bearing cells in both T cells and B cells from SLE patients. Especially, DNA binding B cells, which exclusively produced anti-DNA antibodies, expressed large amounts of Fas ligands. Therefore, like immune-privileged tissues, the excessively expressed Fas ligands on self-reactive lymphocytes may protect themselves from Fas-mediated apoptosis, resulting in the accumulation of self-reactive lymphocytes in SLE patients.Furthermore, Wefound circulating autoantibodies against Fas ligands in patients with SLE.The autoantibodies interfered with Fas and Fas ligand interaction in vitro, suggesting that this is alternative mechanism to lead to the insufficient Fas-mediated elimination of autoreactive lymphocytes.

Fas-Fas配体（FasL）相互作用通过自身反应性淋巴细胞凋亡维持免疫耐受。事实上，具有Fas或Fas配体突变的小鼠发展狼疮样自身免疫性疾病。应用RT-PCR和免疫印迹技术检测了系统性红斑狼疮（SLE）患者外周血淋巴细胞（PBL）Fas配体的表达。我们发现SLE患者外周血淋巴细胞组成型表达Fas配体，而正常人外周血淋巴细胞除非在体外刺激，否则不表达Fas配体。流式细胞仪分析显示SLE患者T细胞和B细胞中均存在Fas配体。特别是，DNA结合B细胞，专门产生抗DNA抗体，表达大量的Fas配体。因此，与免疫赦免组织一样，自身反应性淋巴细胞上过度表达的Fas配体可能会保护自身免受Fas介导的凋亡，导致SLE患者体内自身反应性淋巴细胞的积累。此外，我们在SLE患者体内发现了抗Fas配体的自身抗体，这些自身抗体在体外干扰Fas和Fas配体的相互作用，提示这是导致Fas介导的自身反应性淋巴细胞消除不足的替代机制。

项目成果

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