Enhanced propensity of T lymphocytes in patients with systemic lupus erythematosus to apoptosis in the presence of tumour necrosis factor alpha

Objective: To determine the effect of inflammation through exposure to tumour necrosis factor (TNF) on Tlymphocytes in patients with systemic lupus erythematosus (SLE). Methods: We studied the effect of TNF on T-lymphocyte apoptosis in patients with SLE, rheumatoid arthritis (RA), and in healthy controls. Apoptosis of CD4 and CD8 Tlymphocytes and naive and memory subpopulations was determined by flow cytometry using 7-amino-actinomycin D (7AAD) and propidium iodide (PI). In SLE, apoptosis was studied in patients with active and inactive disease and in patients on different medications. Results: TNF enhanced apoptosis of anti-CD3-activated Tlymphocytes. The percentage of apoptotic cells was significantly higher in Tlymphocytes from patients with SLE than RA patients and healthy controls. After 3 days of culture, 38% of CD4+ and 37% of CD8+ cells from SLE patients underwent apoptosis in the presence of TNF compared with 25% CD4+ and 26% CD8+ Tcells from the controls (p0.001). In healthy controls, more memory than naive Tlymphocytes underwent apoptosis. By contrast, in patients with SLE, more naive Tcells underwent apoptosis with TNF (p0.01). Enhanced apoptosis of Tcells in SLE was independent of disease activity or medication. Finally, inhibition experiments showed that apoptosis in the presence of TNF was only partly blocked with anti-Fas ligand (FasL) antibody. Conclusions: This study demonstrates that Tlymphocytes in patients with SLE are more prone to apoptosis in the presence of TNF than Tlymphocytes from healthy controls. Defects in TNF signalling pathways rather than distribution of TNF receptors (TNFRs) probably explain the enhanced apoptosis in SLE.