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)alpha on T lymphocytes in patients with systemic lupus erythematosus (SLE).

METHODS

We studied the effect of TNFalpha 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

TNFalpha 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 TNFalpha 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 TNFalpha (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 TNFalpha 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 TNFalpha than T lymphocytes from healthy controls. Defects in TNFalpha signalling pathways rather than distribution of TNF receptors (TNFRs) probably explain the enhanced apoptosis in SLE.