The Replacement of Monocytes and Interleukin-1 by Phorbol Ester in Lectin-Induced Proliferation of Human Thymocytes and T Cells

Small human thymocytes isolated by counterflow centrifugal elutriation (CCE) failed to respond to lectins, and therefore they were considered to represent the immature thymocyte (IT) population. In addition, these IT also failed to respond to the tumor promotor 12-0-tetradecanoyl-13 acetate (TPA). Proliferation of the IT was induced if in addition to lectins irradiated allogeneic monocytes, crude interleukin-1 (IL-1) preparations or TPA at concentrations of 1–10^?3 µg/ml were added. Allogeneic monocytes, IL-1 or TPA also acted similarly in their synergistic effects with lectins (at concentrations that induced optimal proliferation) in the proliferative responses of unfractionated thymocytes (UT) and the medium sized to large thymocytes (MLT) which represent the mature thymocyte compartment. Irradiated autologous monocytes or TPA were also found to act in a similar synergistic way with lectins at suboptimal concentrations in the proliferation of mature T cells. These results indicate that TPA mimics the signal provided by monocytes or IL-1 in the mitogenesis of human thymocytes and mature T cells. However, at optimal lectin concentrations autologous monocytes were found to restore the reduced mature T-cell responses, whereas in contrast TPA caused strong reductions in the ³H-thymidine (³H-TdR) uptake of these cells. The mechanism of this depressed ³H-TdR uptake remains unclear, but our data so far indicate that metabolites of TPA are toxic for those T cells that have relatively large quantities of lectins bound to their membranes, since the same metabolites had no toxic effects on mature T cells activated with suboptimal lectin concentrations.