The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/1/189/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 189-196

Articles

The Common Cytokine Receptor {gamma} Chain Plays an Essential Role in Regulating Lymphoid Homeostasis

Hiroshi Nakajima*, Elizabeth W. Shores{ddagger}, Masayuki Noguchi*, and Warren J. Leonard*

From the * Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892; and the {ddagger} Division of Hematologic Products, Food and Drug Administration, Bethesda, Maryland 20892

In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor {gamma} chain ({gamma}c), and it was previously shown that {gamma}c-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4+ T cells, the majority of which have a phenotype typical of memory/activated cells. When {gamma}c-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4+ T cells from {gamma}c-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of {gamma}c-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4+ T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although {gamma}c-independent signals are sufficient to mediate expansion of CD4+ T cells in these mice, {gamma}c-dependent signals are required to regulate the fate of activated CD4+ T cells, underscoring the importance of {gamma}c-dependent signals in controlling lymphoid homeostasis.

Address correspondence to Warren J. Leonard, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Building 10, Room 7N244, 9000 Rockville Pike, Bethesda, MD 20892.

H. Nakajima was supported in part by Japan Society for the Promotion of Science and The Naito Foundation.

1Abbreviations used in this paper: {gamma}c, common cytokine receptor {gamma} chain; PI, propidium iodide; TUNEL, terminal deoxynucleotide transferase (TdT)- dUTP nick end–labeling; XSCID, X-linked severe combined immunodeficiency.


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