Generation of suppressor cells by aggregated human globulin

We have studied the capacity of aggregated human globulin, a model for immune complexes, to induce suppressor cells which modulate a predominantly T cell response, i.e. the proliferative response of autologous mononuclear cells to concanavalin A. We utilized a soluble aggregated human globulin preparation depleted of both high molecular weight (greater than 4 x 10(6) daltons) insoluble aggregates and monomeric IgG. The mean per cent suppression induced by mononuclear cells preincubated with aggregated human globulin for 96 hr was 39 +/- 8%; monomeric IgG did not induce significant suppression (4 +/- 6%). We found a close correlation between the magnitude of suppression induced by preincubation for 96 hr with aggregated human globulin and that induced by preincubation with concanavalin A. Kinetic analysis indicated that suppressor cell induction by aggregated human globulin required 48 hr of preincubation; suppressor cell induction by concanavalin A required 24 hr. Aggregated human globulin-induced suppression was not associated with DNA synthesis as measured by 3H-thymidine uptake. The findings suggest that immune complexes can modulate immunoregulation.