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Blood, 15 March 2004, Vol. 103, No. 6, pp. 1985-1994.
Prepublished online as a Blood First Edition Paper on October 30, 2003November 20, 2003; DOI 10.1182/blood-2003-06-2126.


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Submitted June 27, 2003
Accepted October 19, 2003

Overexpression of IL-7R{alpha} provides a competitive advantage during early T-cell development

Yasmina Laouar, I Nicholas Crispe, and Richard A Flavell*

Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Howard Hughes Medical Institute, New Haven, CT, USA
David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA

* Corresponding author; email: richard.flavell{at}yale.edu.

Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the IL-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 over-expression of IL-7R{alpha} in the early T-cell compartment from AKR/J mice, which 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 using RT-PCR. This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL+ cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over normal B10.BR 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.


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