The Journal of Experimental Medicine
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Published online 14 April 2003 doi:10.1084/jem.20021847
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© Rockefeller University Press, 0022-1007/2003/4/967 $5.00
The Journal of Experimental Medicine, Volume 197, Number 8, 967-976

In Vivo Survival and Homeostatic Proliferation of Natural Killer Cells

Martin Prlic1,3, Bruce R. Blazar1,2,4, Michael A. Farrar1,2,3 and Stephen C. Jameson1,2,3

1 Center for Immunology, University of Minnesota, Minneapolis, MN 55455
2 Cancer Center, University of Minnesota, Minneapolis, MN 55455
3 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455
4 Department of Pediatrics and Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455

Address correspondence to Stephen C. Jameson, 6-110 BSBE, 312 Church St. SE, Minneapolis, MN 55455. Phone: 612-625-1496; Fax: 612-625-2199; E-mail: james024{at}umn.edu

While the specificity and development of natural killer (NK) cells have been intensely studied, little is known about homeostasis of the mature NK population. Here we show that mouse NK cells undergo homeostatic proliferation when transferred into NK-deficient Rag-/- {gamma}C-/- hosts. Normal NK functional activity is maintained during this process, although there are some changes in NK phenotype. Using cell sorting, we demonstrate that mature (Mac-1hi) NK cells undergo homeostatic proliferation in an NK-deficient environment, yet immature (Mac-1lo) NK cells also proliferate in such hosts. We find that mature NK cells survive but do not proliferate in hosts which possess an endogenous NK pool. However, we go on to show that mature NK survival is critically dependent on interleukin (IL)-15. Surprisingly, NK survival is also compromised after transfer of cells into IL-15R{alpha}-/- mice, implying that IL-15 responsiveness by bystander cells is critical for NK maintenance. These data imply that, similar to T cells, homeostasis of the NK pool is much more dynamic than previously appreciated and this may be relevant to manipulation of NK cells for therapeutic purposes.

Key Words: IL-15 • lymphopenia • cytokines • homeostasis


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