Objective. To determine whether impaired generation of polyclonal T cell cytolytic activity is over‐represented in systemic lupus erythematosus (SLE) compared with other rheumatologic diseases and whether such impaired generation of cytolytic activity waxes and wanes with disease activity and/or changes in medications.

Methods. Peripheral blood mononuclear cells from 84 SLE patients, 55 rheumatologic disease (RD) controls, and 44 normal subjects were stimulated with anti‐CD3 monoclonal antibody, maintained in interleukin‐2, and assayed for cytolytic activity against ⁵¹Cr‐labeled Daudi target cells.

Results. Generation of cytolytic activity was significantly lower in SLE patients than in either RD or normal controls. Abnormal cytolytic responses in SLE could not be attributed to the patient's sex, race, age, disease activity, or antirheumatic medications (including corticosteroids and cytotoxics), although both SLE and RD patients taking azathioprine (AZA) manifested lower responses than did corresponding patients not taking AZA. Abnormal cytolytic activity reflected, in large measure, impaired cytolytic activity of CD8+ T cells. No significant difference in the generation of cytolytic activity between RD and normal controls was detected.

Conclusion. Impaired generation of polyclonal T cell cytolytic activity may be a predisposing factor in the development of SLE.