The Journal of Experimental Medicine
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Published 17 June 2002. doi:10.1084/jem.20020066
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© Rockefeller University Press, 0022-1007/2002/6/1523/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 12, June 17, 2002 1523-1532

Interleukin (IL)-15 and IL-7 Jointly Regulate Homeostatic Proliferation of Memory Phenotype CD8+ Cells but Are Not Required for Memory Phenotype CD4+ Cells

Joyce T. Tan, Bettina Ernst, William C. Kieper, Eric LeRoy, Jonathan Sprent and Charles D. Surh

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Charles D. Surh, Dept. of Immunology, IMM26, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 858-784-2006; Fax: 858-784-8227; E-mail: csurh{at}scripps.edu

The overall size and composition of the pool of naive and memory T cells are tightly regulated by homeostatic mechanisms. Recent work has shown that homeostasis of naive T cells is controlled by two factors, self-major histocompatibility complex (MHC)/peptide ligands and a cytokine, interleukin (IL)-7. In particular, contact with these two factors is required for naive CD4+ and CD8+ cells to undergo "homeostatic" proliferation, i.e., proliferation induced as a consequence of severe T cell depletion. In contrast to naive T cells, the factors that drive memory T cells to undergo homeostatic proliferation are poorly understood. To address this issue, purified memory phenotype CD4+ and CD8+ cells from normal mice were adoptively transferred into various gene-knockout mice rendered T cell–deficient by sublethal irradiation. Three findings are reported. First, unlike naive T cells, homeostatic proliferation of memory T cells is largely MHC independent. Second, memory CD8+ cells can utilize either IL-7 or IL-15 to undergo homeostatic proliferation; however, in the absence of both IL-7 and IL-15, homeostatic proliferation fails to occur. Third, unlike memory CD8+ cells, homeostatic proliferation of memory CD4+ cells is independent of IL-7 and IL-15 (also IL-4). Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct.

Key Words: homeostasis • cytokines • memory • T lymphocytes • lymphopenia


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