J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/02/499/08 $2.00
Volume 185 February 1997 499-506

Abnormal Development of Intestinal Intraepithelial Lymphocytes and Peripheral Natural Killer Cells in Mice Lacking the IL-2 Receptor  Chain

By Haruhiko Suzuki,^§ Gordon S. Duncan,^* Hiroaki Takimoto,^§ and Tak W. Mak^*§

From the ^* Amgen Institute,  Ontario Cancer Institute, and ^§ Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada M5G 2C1

The interleukin-2 receptor  chain (IL-2R) is expressed on a variety of hematopoietic cell types, including natural killer (NK) cells and nonconventional T lymphocyte subsets such as intestinal intraepithelial lymphocytes (IEL). However, the importance of IL-2R-mediated signaling in the growth and development of these cells has yet to be clearly established. We have investigated IEL and NK cells in mice deficient for IL-2R and describe here striking defects in the development of these cells. IL-2R^/ mice exhibited an abnormal IEL cell population, characterized by a dramatic reduction in T cell receptor CD8 and T cell receptor lymphocytes. This selective decrease indicates that IEL can be classified into those whose development and/or differentiation is dependent on IL-2R function and those for which IL-2R-mediated signaling is not essential. NK cell development was also found to be disrupted in IL-2R-deficient mice, characterized by a reduction in NK1.1⁺CD3 cells in the peripheral circulation and an absence of NK cytotoxic activity in vitro. The dependence of NK cells and certain subclasses of IEL cells on IL-2R expression points to an essential role for signaling through this receptor, presumably by IL-2 and/or IL-15, in the development of lymphocyte subsets of extrathymic origin.

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