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

Abstract

Objective: To determine the effect of inflammation through exposure to tumour necrosis factor (TNF)α on T lymphocytes in patients with systemic lupus erythematosus (SLE).Methods: We studied the effect of TNFα on T‐lymphocyte apoptosis in patients with SLE, rheumatoid arthritis (RA), and in healthy controls. Apoptosis of CD4 and CD8 T lymphocytes 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: TNFα enhanced apoptosis of anti‐CD3‐activated T lymphocytes. The percentage of apoptotic cells was significantly higher in T lymphocytes 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 TNFα compared with 25% CD4+ and 26% CD8+ T cells from the controls (p<0.001). In healthy controls, more memory than naive T lymphocytes underwent apoptosis. By contrast, in patients with SLE, more naive T cells underwent apoptosis with TNFα (p<0.01). Enhanced apoptosis of T cells in SLE was independent of disease activity or medication. Finally, inhibition experiments showed that apoptosis in the presence of TNFα was only partly blocked with anti‐Fas ligand (FasL) antibody.Conclusions: This study demonstrates that T lymphocytes in patients with SLE are more prone to apoptosis in the presence of TNFα than T lymphocytes from healthy controls. Defects in TNFα signalling pathways rather than distribution of TNF receptors (TNFRs) probably explain the enhanced apoptosis in SLE.