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Role of the Intracellular Domain of IL-7 Receptor in T Cell Development¹

Qiong Jiang^*, Jiaqiang Huang, Wen Qing Li^*, Tiziana Cavinato^*, Jonathan R. Keller and Scott K. Durum^2,*

^* Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231; and Basic Research Program, Science Applications International Corporation-Frederick, National Cancer Institute, Frederick, MD

Signals from the IL-7R are uniquely required for T cell development and maintenance, despite the resemblance of IL-7R to other cytokine receptors and the apparent sharing of common signaling pathways. This unique requirement could either reflect unique expression of IL-7R or IL-7, or it could indicate that the IL-7R delivers unique signals. To determine whether the IL-7R provided unique signals, we exchanged its intracellular domain with that of other cytokine receptors: IL-4R, IL-9R, and prolactin receptor (PRLR). Chimeric receptors were used to reconstitute development of IL-7R^–/– hemopoietic progenitors by transducing the receptors in retroviral vectors. Whereas IL-7R^–/– thymocytes are arrested at the double-negative stage, IL-4R, IL-9R, or PRLR all imparted some progression to the double-positive stage. IL-4R and PRLR gave only small numbers of thymocytes, whereas IL-9R gave robust T cell development and reconstitution of peripheral CD4 and CD8 cells, indicating that it can duplicate many of the functions of IL-7R. However, IL-9R failed to reconstitute rearrangement of the TCR locus or development of T cells. Thus, the IL-7R signals required in the T cell lineage (such as survival and proliferation) are not unique to this receptor, whereas rearrangement of the TCR locus may require a signal that is not shared by other receptors.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute.

² Address correspondence and reprint requests to Dr. Scott K. Durum, Chief, Section of Cytokines and Immunity, Building 560, Room 31-71, Frederick, MD 21702-1201. E-mail address: durums{at}mail.ncifcrf.gov

³ Abbreviations used in this paper: DN, double negative; _c, common -chain; PRLR, prolactin receptor; Epo, erythropoietin; WT, wild type; 5FU, 5-fluorouracil; PI, propidium iodide; Q-PCR, quantitative PCR; SOCS, suppressor of cytokine signaling; m, murine.