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-Chain)-Deficient Hosts Elicits Rapid Homeostatic Proliferation of Naive T Cells via IL-151


* Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037;
Department of Biological Sciences, University of California San Diego, La Jolla, CA 92037; and
Garvan Institute of Medical Research, Sydney, New South Wales, Australia
Homeostatic proliferation for naive T cells is observed readily only under lymphopenic conditions in response to elevated levels of IL-7 and contact with self-MHC/peptide ligands. Homeostatic proliferation occurs at a slow pace and gradually induces the dividing cells to acquire characteristics of memory cells. We describe a novel type of homeostatic proliferation whereby naive T cells proliferate at a significantly faster rate, resembling the proliferation speed induced by foreign Ags, and the expanding cells rapidly differentiate into central memory cells. Remarkably, such rapid homeostatic proliferation is driven by a combination of IL-2 and IL-15, with IL-15 playing a bigger role, and applies for a wide repertoire of CD8+ naive T cells, including many TCR-transgenic lines, even those that fail to undergo IL-7-driven homeostatic proliferation. Thus, naive T cells can be induced to undergo homeostatic proliferation of variable speed with a few members of the common
-chain (CD132) family of cytokines, the speed of proliferation depending on the levels of the particular cytokine involved.
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 U.S. Public Health Service Grants AI045809, AI064586, and AG020186 (to C.D.S.) and AI046710, AI007244, and AG001743 (to J.S.). C.R. was supported by a National Institutes of Health Training Grant T32 AI07244.
2 Address correspondence and reprint requests to Dr. Charles D. Surh, Department of Immunology, IMM-26, The Scripps Research Institute, La Jolla, CA 92037. E-mail address: csurh{at}scripps.edu
3 Abbreviations used in this paper:
c, common
-chain; LN, lymph node; LM, Listeria monocytogenes; TG, transgenic; MHC-I, MHC class I; MHC-II, MHC class II; Treg, regulatory T cell.
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