Induction of suppressor activity by tumor-promoting phorbol esters in primary cultures of lymph node cells

We have observed the induction of suppressor activity in primary cultures of lymphocytes by the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Suppressor activity was detected as the ability of TPA-treated lymphocytes to inhibit proliferation in mixed lymphocyte cultures (MLC). Induction of this activity was dependent on the dose of TPA and was maximal after approximately 12 h of incubation. Neither the induction of the activity, nor the activity itself was inhibited by indomethacin or interleukin 2 (IL2). A comparison of addition of TPA directly to the MLC, addition of TPA pretreated cells as participants in the MLC and addition of cells treated with TPA to induce suppressor activity suggested that the suppressor activity was only one of the ways that TPA could inhibit proliferation. This suppressor activity may account for some of the reported effects of TPA in immunological systems in vitro and suggests that suppressor cells could play a role in TPA-mediated promotion in vivo.