Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development.
Critical 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 alpha beta T-cell development is observed in IL-7- and IL-7R alpha-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-7R alpha 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-7R alpha was revealed by surface staining, and increased IL-7R alpha 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.
Laouar
Yasmina
Y
Section of Immunobiology, Yale University School of Medicine, 300 Ceda St, CAB S-569, New Haven, CT 06520, USA. richard.flavell@yale.edu
Crispe
I Nicholas
IN
Flavell
Richard A
RA
D000818:Animals; D002470:Cell Survival / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D007107:Immune System / Q000196:embryology / Q000503:physiopathology*; D007938:Leukemia / Q000503:physiopathology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D012038:Regeneration / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013945:Thymoma / Q000503:physiopathology*; D013953:Thymus Neoplasms / Q000503:physiopathology*
D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain