SLE 1 - Clin Exp Immunol 2001; 123:127132 Anti-CD3-induced...

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q 2001 Blackwell Science 127 Clin Exp Immunol 2001; 123 :127–132 Anti-CD3-induced and anti-Fas-induced apoptosis in systemic lupus erythematosus (SLE) M. BIJL, G. HORST, P. C. LIMBURG* & C. G. M. KALLENBERG Department of Clinical Immunology and * Department of Rheumatology, University Hospital, Groningen, The Netherlands (Accepted for publication 14 September 2000) SUMMARY Disturbances in apoptosis or in the clearance of apoptotic material might result in increased presentation of autoantigens which could be relevant to the pathogenesis of SLE. Data concerning defects in apoptosis in SLE are conflicting. To determine whether intrinsic defects in apoptosis induction occur in SLE irrespective of disease activity, we examined anti-CD3 and anti-Fas-induced apoptosis in vitro in SLE patients with inactive disease. Isolated peripheral blood lymphocytes (PBL) from 13 SLE patients and 14 healthy controls were incubated with anti-CD3, and, subsequently, after up-regulation of membrane Fas following anti-CD3 incubation, with anti-Fas. Expression of Fas and levels of apoptosis as detected by annexin V and propidium iodide staining were assessed by flow cytometry before and after the respective incubations. Fas expression on freshly isolated lymphocytes of SLE patients was increased whereas levels of circulating apoptotic cells were comparable between patients and controls. Stimulation with anti-CD3 resulted in up-regulation of membrane Fas in patients and in controls. In vitro induction of apoptosis by anti-CD3 as well as by anti-Fas occurred both in SLE patients and controls, and was higher in SLE patients after incubation with anti-CD3 as well as with anti-Fas. We conclude that Fas expression and in vitro induction of apoptosis are increased in SLE even in the absence of disease activity. Keywords systemic lupus erythematosus apoptosis lymphocytes INTRODUCTION SLE, the prototype of a systemic autoimmune disease, is associated with various immunological abnormalities such as increased number of activated B lymphocytes and production of multiple autoantibodies. Autoantibody production has been shown to be selective, T cell-dependent, and antigen-driven. Even in inactive disease peripheral blood lymphocytes (PBL) show signs of activation [1]. Persistent autoantigen presentation may be responsible for this continuous state of lymphocyte activation. Presentation of cryptic antigens and modification, including cleavage and phosphorylation, can occur during apoptosis, resulting in autoantibody production [2,3]. Therefore, it can be speculated that increased apoptosis of peripheral blood mono- nuclear cells (PBMC) contributes to persistent lymphocyte activation and autoantibody production in SLE. Indeed, in vitro as well as in vivo , the level of apoptosis of PBMC of lupus patients has been shown to be elevated [4–7]. It has been suggested that this is due to increased in vivo activation of PBMC in SLE resulting in increased activation-induced cell death [5].
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SLE 1 - Clin Exp Immunol 2001; 123:127132 Anti-CD3-induced...

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