In vivo survival and homeostatic proliferation of natural killer cells

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

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-/- γC-/- 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-15Rα-/- 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.

Original languageEnglish (US)
Pages (from-to)967-976
Number of pages10
JournalJournal of Experimental Medicine
Volume197
Issue number8
DOIs
StatePublished - Apr 21 2003

Keywords

  • Cytokines
  • Homeostasis
  • IL-15
  • Lymphopenia

Fingerprint

Dive into the research topics of 'In vivo survival and homeostatic proliferation of natural killer cells'. Together they form a unique fingerprint.

Cite this