title: Synergistic effects of interleukin-7 and pre-T cell receptor signaling in human T cell development.
abstract: The role of IL-7 in pre-T cell receptor (TCR) signaling during human T cell development is poorly understood. To study this, we engineered Molt3, a T cell progenitor T-acute lymphoblastic leukemia cell line, using lentiviral IL-7 receptor α (IL-7Rα) to serve as a model system. IL-7 promoted pre-TCR activation in IL-7Rα(hi) Molt3 as illustrated by CD25 up-regulation after anti-CD3 stimulation. Anti-CD3 treatment activated Akt and Erk1/2 signaling pathways as proven using specific inhibitors, and IL-7 further enhanced both signaling pathways. The close association of IL-7Rα with CD3ζ in the pre-TCR complex was illustrated through live imaging confocal fluorescence microscopy. These results demonstrate a direct and cooperative role of IL-7 in pre-TCR signaling.
authors.affiliation: Department of Molecular Genetics, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Ekta S
authors.initials: ES
authors.lastname: Patel
authors.forename: Lung-Ji
authors.initials: LJ
authors.lastname: Chang
mesh_terms: D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D015851:Interleukin-7 / Q000378:metabolism*; D019169:Jurkat Cells; D016086:Lentivirus / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000821:virology
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium