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.