Media conditioned by human leukemic T-cells induce expression of IL2 receptors and proliferation of normal T lymphocytes

Peripheral blood T-colony-forming cells (T-CFC) from patients with T-cell acute lymphoblastic leukemias (T-ALL) and T-cell non-Hodgkin lymphomas (T-NHL) can generate colonies in methylcellulose in the absence of added growth factors and/or mitogenic stimulation. In the present study, we show that media conditioned (LCM) by unstimulated mononuclear cells (MNC) from these patients can induce proliferation (proliferating inducing activity; PIA) and promote colony growth (T-cell colony promoting activity; T-CPA) of normal T lymphocytes in the absence of any other mitogenic stimulation. Preincubation of normal E+ lymphocytes with some TCPA+, PIA−-LCM for 48 hr leads to IL2-induced cell proliferation in the absence of any other stimulation. Moreover, staining of the cells with anti-Tac monoclonal antibody (Mab) reveal 9%-26% Tac+ cells. Both PIA and IL2 receptor-inducing activities were abrogated by treatment of LCM with proteolytic enzymes or by heating at 47°C for 30 min. Modulation of the T3 molecule by OKT3 MAb on normal E+ cells did not abrogate the capacity of LCM to induce expression of IL2-receptors, suggesting that this activity was not mediated by triggering the Ti-T3 molecular complex. These activities were detected in media conditioned by both unfractionated MNC and blast-enriched cell fractions, and their production required DNA and RNA synthesis by actively dividing cells. Taken together, these findings indicate that human leukemic T cells spontaneously release activites which can activate normal resting T lymphocytes.