Thymic epithelial cells promote survival of human T-cell acute lymphoblastic leukemia blasts: the role of interleukin-7

Abstract

BACKGROUND AND OBJECTIVES: T-cell lymphoblastic leukemia (T-ALL) cells originate within the thymus from the clonal expansion of T cell precursors. Among thymic stromal elements, epithelial cells (TEC) are known to exert a dominant inductive role in survival and maturation of normal, immature T-cells. In this study we explored the possible effect of TEC on T-ALL cell survival and analyzed the role of interleukin-7 (IL-7) within the microenvironment generated by T-ALL-TEC interactions. DESIGN AND METHODS: T-ALL blasts derived from 10 adult patients were cultured with TEC obtained from human normal thymuses. The level of blast apoptosis was measured by annexin V-propidium iodide co-staining and flow cytometry. The proliferative response of leukemic cells to interaction with TEC was evaluated by thymidine incorporation at various time intervals of culture. To assess the role of IL-7, lympho-epithelial co-cultures were carried out in the presence of anti-IL-7 or anti IL-7R blocking antibodies and the level of apoptosis of T-ALL blasts was analyzed. RESULTS: When T-ALL cells were cultured in the presence of TEC monolayers, the percentage of viable cells increased significantly and this survival was sustained with time in culture. In addition, the interaction with TEC induced a considerable proliferative response in T-ALL cells (15-fold greater than that of the control cells after 7 days of culture). The presence of IL-7 or IL-7R blocking antibodies in lympho-epithelial co-cultures consistently reduced the TEC-mediated apoptosis inhibition in T-ALL blasts (70% decrease). INTERPRETATION AND CONCLUSIONS: These results point to the role of thymic epithelium in the regulation of T blast survival. In addition, they show that interaction between IL-7 and its receptor has the major role in modulating T-ALL survival within the microenvironment generated by the T-ALL/TEC interaction.