Requirement for both the CD3/T cell receptor complex and the CD2/lymphocyte function-associated antigen-3 adhesion system in monocyte-independent T cell activation by oxidized erythrocytes

Recent reports have shown that human T lymphocytes can be activated in vitro by desialyzed oxidized erythrocytes (DOE) in a monocyte-independent fashion. These findings suggest that, in addition to providing the activating stimulus, DOE may also fulfill accessory cell roles normally supplied by monocytes in T cell activation. DOE may thus be a useful substitute for antigen-presenting accessory cells in studies of T cell activation. This report describes experiments conducted to determine if T cell activation by DOE involves cell surface structures known to play a role in antigen-induced T cell activation. T cell stimulation by DOE was blocked by anti-CD3 monoclonal antibody, suggesting that perturbation of the CD3/T cell antigen receptor complex on T cells is required for activation. Activation was also blocked by anti-CD2 monoclonal antibody, indicating involvement of the CD2/LFA-3 adhesion system. Since DOE and monocytes both express LFA-3, the role of LFA-3 on DOE in T cell activation was assessed. DOE pretreated with anti-LFA-3 monoclonal antibody induced markedly lower levels of T cell proliferation. As further evidence for LFA-3 involvement, DOE prepared from 5 patients with paroxysmal nocturnal hemoglobinuria (PNH), known to exhibit deficient LFA-3 expression, were also deficient in T-cell stimulatory activity. These findings illustrate that T cell activation by DOE requires many of the surface structures involved in activation by antigen-bearing accessory cells, and may thus serve as a useful model for studies of T cell activation.