In vitro generation of adherent mononuclear suppressor cells to Toxoplasma antigen.

Adherent mononuclear cells have been found to suppress the lymphocyte proliferation, of T lymphocytes of patients with various chronic infections, to pathogen-specific antigens. To explore mechanisms involved in the generation of these suppressor cells, we established an in vitro method for the generation of suppressor-adherent mononuclear cells. Adherent mononuclear cells separated from mononuclear cells from subjects with serological evidence of chronic Toxoplasma infection could be induced, by preincubation with Toxoplasma antigen for 8 days, to suppress the proliferative response to autologous mononuclear cells to Toxoplasma antigen (TA) (mean suppression = 47%) and tetanus toxoid (TT) (mean suppression = 39%) compared to the proliferative response of autologous mononuclear cells co-cultured with no antigen. When adherent cells were removed after 1-day culture there was no significant suppression of the lympho-proliferative response to TA or TT. Induction of the adherent suppressor cell depended on the presence of CD4-positive T cells and not CD8-positive T cells. Adherent suppressor cells acted directly on the proliferative response of CD4 cells to antigen. The adherent cells contained 90 +/- 5% esterase-positive cells. In cell-mixing experiments, equal numbers of CD8-positive T cells pretreated in a similar manner did not have a suppressive effect. However, pretreated CD4-positive cells did have a suppressive effect at higher concentrations of cells than found in the adherent cells. Indomethacin did not alter the suppressive effect. These studies demonstrate the induction of adherent suppressor cells in vitro and implicate the macrophage and CD4-positive T cells as the suppressor cells.