Inhibition of human T cell response to staphylococcal enterotoxin B by prior ligation of surface CD4 molecules.
The mechanisms whereby anti-CD4 monoclonal antibodies can block human peripheral blood lymphocyte response to staphylococcal enterotoxin B (SEB) were investigated. Preincubation of peripheral blood mononuclear cells (PBMC) with anti-CD4 mAbs resulted in a profound inhibition of SEB-induced DNA synthesis, while simultaneous addition of antibody and superantigen did not reproducibly decrease the proliferative response. Inhibition was achieved at a very low antibody concentration (0.1 microgram/ml). It was not increased by cross-linking of anti-CD4 mAb nor mediated by Fc-dependent signals as F(ab')2 antibody fragments were as effective as intact antibodies. Inhibition of proliferation was associated with a profound diminution of IL-2 and IFN-gamma secretion, CD25 (the alpha chain of IL-2 receptor) expression, and blast transformation. Stimulation by SEB after prior ligation of surface CD4 proteins by antibodies was associated with an increased percentage of lymphocytes with chromatin condensation and nuclear fragmentation. It was concluded that stimulation of mature peripheral T cells by SEB through T cell receptors induces an apoptotic signal providing that a small proportion of surface CD4 molecules has interacted with antibodies or F(ab')2 fragments before stimulation by SEB, while simultaneous addition of SEB and anti-CD4 mAb does not prevent the development of a complete activation program in this system. Possible implications of these observations regarding selective clonal deletion of autoreactive T cells by administration of anti-CD4 mAbs in patients with auto-immune diseases are discussed.