Induction of IL-2 production, IL-2 receptor expression and proliferation of T3- T-PLL cells by phorbol ester.

Leukemic T cells from the peripheral blood of a patient with T-prolymphocytic leukemia (T-PLL) were investigated for their potential to differentiate in vitro upon exposure to 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The T-PLL cells, identified as typical PLL cells by nuclear morphology, were typed as E+slg-OKT1+3-4+6-8-11+ cells lacking reactivity with OKI-1 or OKM-1. In addition, between 3% and 10% of the cells reacted with monoclonal antibodies against T10. In contrast to normal T cells, the T-PLL cells could not be induced to proliferate by mitogenic lectins or alloantigens in the presence or absence of human interleukin-1 (IL-1), interleukin-2(IL-2) or allogeneic monocytes and did not produce IL-2. They also failed to proliferate in response to TPA or TPA in the presence of phytohemagglutinin (PHA), but under these conditions T-PLL cells secreted high levels of IL-2 activity. Incubation in the presence of PHA + TPA or TPA for 48 h induced T-PLL cells to become blasts exhibiting enhanced protein synthesis, and induced a 10-fold increase in the percentage of cells reactive with monoclonal antibodies against T10. At the same time, about 15% of the cells developed receptors for IL-2 as monitored by their reactivity with anti-Tac monoclonal antibody. Washing of these T-PLL cells to remove TPA resulted in the induction of proliferation upon subsequent culture in the presence of IL-2 or in medium only. Since proliferating T-PLL cells still failed to express T3 antigens, it was concluded that these leukemic cells represent a T-cell differentiation stage or a T-cell subset which can be activated via a T3-independent pathway.