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J. Exp. Med.
Volume 186, Number 2, July 21, 1997 331-336

BRIEF DEFINITIVE REPORT:
Distinct Roles for Signals Relayed through the Common Cytokine Receptor gamma  Chain and Interleukin 7 Receptor alpha  Chain in Natural T Cell Development

By Alina Boesteanu,* A. Dharshan De Silva,* Hiroshi Nakajima,Dagger Warren J. Leonard,Dagger Jacques J. Peschon,§ and Sebastian Joyce*

From the * Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Dagger  Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; and § Immunex Research and Development Corporation, Seattle, Washington 98101

The commitment, differentiation, and expansion of mainstream alpha /beta T cells during ontogeny depend on the highly controlled interplay of signals relayed by cytokines through their receptors on progenitor cells. The role of cytokines in the development of natural killer (NK)1+ natural T cells is less clearly understood. In an approach to define the role of cytokines in the commitment, differentiation, and expansion of NK1+ T cells, their development was studied in common cytokine receptor gamma  chain (gamma c) and interleukin (IL)-7 receptor alpha  (IL-7Ralpha )-deficient mice. These mutations block mainstream alpha /beta T cell ontogeny at an early prethymocyte stage. Natural T cells do not develop in gamma c-deficient mice; they are absent in the thymus and peripheral lymphoid organs such as the liver and the spleen. In contrast, NK1+ T cells develop in IL-7Ralpha -deficient mice in the thymus, and they are present in the liver and in the spleen. However, the absolute number of NK1+ T cells in the thymus of IL-7Ralpha -deficient mice is reduced to ~10%, compared to natural T cell number in the wild-type thymus. Additional data revealed that NK1+ T cell ontogeny is not impaired in IL-2- or IL-4-deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development. From these data, we conclude that commitment and/or differentiation to the NK1+ natural T cell lineage requires signal transduction through the gamma c, and once committed, their expansion requires signals relayed through the IL-7Ralpha .


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