Anti-CD3-induced and anti-Fas-induced apoptosis in systemic lupus erythematosus (SLE).
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.
Bijl
M
M
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
Horst
G
G
Limburg
P C
PC
Kallenberg
C G
CG
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D013194:Staining and Labeling; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology*
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017252:CD3 Complex; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor; D011239:Prednisolone