DEFECTIVE CD3-MEDIATED CELL-DEATH IN ACTIVATED T-CELLS FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS - ROLE OF DECREASED INTRACELLULAR TNF-ALPHA

Activation-induced cell death (AICD) plays an important role in the re gulation of the immune response by eliminating preactivated and potent ially autoreactive cells. To elucidate possible abnormalities of AICD in human systemic lupus erythematosus (SLE), we studied AICD in activa ted T cells from patients with SLE and normal controls. CD3-mediated c ell death was determined in short-term T cell lines by flow cytometry using propidium iodide staining and analysis of DNA subdiploid peak po pulations. It was found to be significantly lower in T cells from SLE patients compared to cells from normal controls. Anti-Fas mAb-mediated cell death was similar in SLE and control cell lines. CD3-mediated AI CD could be blocked in control and SLE T cell lines by an IgG anti-Fas mAb. Indirect immunofluorescence analysis showed statistically signif icantly less intracellular TNF-alpha in SLE T cells than in control ce lls. These data show that activated T cells from patients with SLE are relatively resistant to a TCR-mediated death stimulus although they d isplay intact anti-Fas mAb-mediated cell death. Defective antigen-medi ated cell death can contribute to increased numbers of activated autor eactive cells in lupus patients. (C) 1996 Academic Press, Inc.