Modification by biological products of the generation of suppressor cells in culture.

This report describes the effects of prostaglandin E2 (PGE2), indomethacin, and human prealbumin on the generation of culture-induced and allo-antigen-induced suppressor cells. The ability of the suppressor cells to affect cell-mediated immunity (CMI) generation cultures was assessed by 3H-thymidine uptake and cell-mediated lympholysis (CML). The generation of culture-induced suppressor cells is dependent on the fetal calf-serum (FCS) used in the medium and at least 4 days are necessary for their generation. Suppression is totally abolished by 2,000r X-irradiation of suppressor cells prior to their testing in CMI generation cultures. Spleen cells cultured in the presence of 0.03 to 3 microM PGE2 are not suppressive, while 3 nM PGE2 only partially abolishes their suppressive activity. Indomethacin has little effect on the development of this suppressor cell activity. Spleen cells cultured in the presence of human prealbumin have augmented cellular proliferation but do not develop suppressor cell activity. Alloantigen-activated cells added to CMI generation cultures suppress cellular proliferation (3H-thymidine uptake), but suppress CML development only after X-irradiation. PGE2 inhibits the proliferation of alloantigen-activated cells in a dose dependent manner. The ability of PGE2 to abolish their suppressive activity (after X-irradiation) in CMI generation cultures is directly proportional to its effects on cell proliferation. Indomethacin augments the proliferation of alloantigen-activated cells but does not further augment suppression. Human prealbumin augments the cellular proliferation of alloantigen-activated suppressor cell culture systems, but does not affect the generation of alloantigen-activated suppressor activity.