title: Thymic epithelial cells promote survival of human T-cell acute lymphoblastic leukemia blasts: the role of interleukin-7.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  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.
authors: Department of Clinical and Experimental Medicine, Section of Haematology, University of Verona, Verona, Italy. mariateresa.scupoli@univr.it
authors: Maria T
authors: MT
authors: Scupoli
authors: Fabrizio
authors: F
authors: Vinante
authors: Mauro
authors: M
authors: Krampera
authors: Carlo
authors: C
authors: Vincenzi
authors: Gianpaolo
authors: G
authors: Nadali
authors: Francesca
authors: F
authors: Zampieri
authors: Mary A
authors: MA
authors: Ritter
authors: Efrem
authors: E
authors: Eren
authors: Francesco
authors: F
authors: Santini
authors: Giovanni
authors: G
authors: Pizzolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured / Q000378:metabolism; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000502:physiology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D008297:Male; D014411:Neoplastic Stem Cells / Q000166:cytology*; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D015851:Interleukin-7; D020395:Receptors, Interleukin-7