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

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Abstract
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+ sIg−OKTI+3−4+6−8−11+ cells lacking reactivity with OKI‐I or OKM‐l. 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‐l (IL‐I), 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.