Overexpression of IL-7Rα provides a competitive advantage during early T-cell development

Abstract

AbstractCritical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre–T-cell antigen receptor. Although αβ T-cell development is observed in IL-7– and IL-7Rα–deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7Rα that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7Rα was revealed by surface staining, and increased IL-7Rα mRNA was documented by using reverse transcriptase–polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL+ (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]–fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.