| Research Abstract |
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.
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