The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/1/197/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 197-206


Articles

Peripheral Expression of Jak3 Is Required to Maintain T Lymphocyte Function

Daniel C. Thomis and Leslie J. Berg

From the Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138

The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine receptors that utilize the common {gamma} chain ({gamma}c), such as those for IL-2, IL-4, IL-7, IL-9, and IL-15. Recent studies of Jak3-deficient mice and humans have demonstrated that Jak3 plays a critical role in B and T lymphocyte maturation and function. The T lymphocyte defects in Jak3-deficient mice include a small thymus, a decrease in peripheral CD8+ cells, an increase in the surface expression of activation markers, and a severe reduction in proliferative and cytokine secretion responses to mitogenic stimuli. To determine whether the peripheral T lymphocyte defects result from aberrant maturation in the thymus or from the absence of Jak3 protein in peripheral T cells, we generated reconstituted mice that express normal levels of Jak3 protein in the thymus but lose Jak3 expression in peripheral T cells. Jak3 expression in the thymus restores normal T cell development, including CD8+, {gamma}{delta}, and natural killer cells. However, the loss of Jak3 protein in peripheral T cells leads to the Jak3–/– phenotype, demonstrating that Jak3 is constitutively required to maintain T cell function.


Address correspondence to Leslie J. Berg, Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138.

This work was supported by the American Cancer Society (L.J. Berg) and the National Institutes of Health (L.J. Berg). D.C. Thomis is a SmithKline Beecham Pharmaceuticals Fellow of the Life Sciences Research Foundation.

1Abbreviations used in this paper: {gamma}c, IL-2 receptor {gamma} chain; XCID, moderate combined immunodeficiency disease.


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