Low responsiveness to the anti Leu 4 antibody by T cells from patients with active systemic lupus erythematosus.

It has been widely accepted that murine monoclonal antibodies against the CD 3 antigen have mitogenic effects on human T cells which mimic antigen binding via the T cell receptors. We report that T cells from patients with active systemic lupus erythematosus cannot respond to anti Leu 4 antibody, an anti CD 3 murine monoclonal antibody of the subclass IgG1. It was observed that T cells from patients with the active disease expressed as much of the Leu 4 and OKT 3 epitopes as compared to high responders, and sera from active patients could not change the expression of the Leu 4 epitope. Similarly, the low responsiveness could not be attributed to suppressor T cells, poor production of IL 2 or less expression of the IL 2 receptor. The accessory nonrosetting mononuclear leucocytes from high responders could convert the low responsiveness of these patients to high, whereas the accessory cells from active patients failed to help the responses of T cells from high responders. Likewise, exogenous IL 1 and anti Leu 4 antibody bound to Sepharose beads independently or cooperatively failed to propagate T cells from low responders. We suggest that the low response to anti Leu 4 antibody as demonstrated in the T cells of patients with active SLE may be due in part to the impairment of the secondary signals, distinct from IL 1, between helping accessory cells and responding T cells, or to the dysfunction of intracellular transmission of stimulation, and may play significant roles in the pathogenesis of SLE.