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.
Section of Immunobiology, Yale University School of Medicine, 300 Ceda St, CAB S-569, New Haven, CT 06520, USA. richard.flavell@yale.edu
Yasmina
Y
Laouar
I Nicholas
IN
Crispe
Richard A
RA
Flavell
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