Fas ligands peripheral lymphocytes from patients with systemic lupus erythematosus

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，携带Fas或Fas配体突变的小鼠会患上狼疮样自身免疫性疾病。本文采用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）上Fas配体的表达。我们发现，在大多数SLE患者中，PBL组成性地表达Fas配体，而来自正常供体的PBL除非在体外刺激，否则从不表达Fas配体。流式细胞术分析显示，SLE患者的T细胞和B细胞中均含有Fas配体。特别是DNA结合的B细胞，它只产生抗DNA抗体，表达大量的Fas配体。因此，与免疫特权组织一样，自身反应性淋巴细胞上过度表达的Fas配体可能保护自身免受Fas介导的凋亡，从而导致SLE患者自身反应性淋巴细胞的积累。此外，我们在SLE患者中发现了针对Fas配体的循环自身抗体。在体外，自身抗体干扰Fas和Fas配体的相互作用，表明这是导致Fas介导的自身反应性淋巴细胞消除不足的另一种机制。

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.