Chronic lymphocytosis of functionally immature natural killer cells

Anthony R. French, Sungjin Kim, Todd A. Fehniger, Jennifer R. Pratt, Liping Yang, Yun Jeong Song, Michael A. Caligiuri, Wayne M. Yokoyama

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: The development of natural killer (NK) cells in the bone marrow is not well characterized. We recently described a mouse (referred to as an NK cell-deficient [NKD] mouse) with a selective deficiency in NK cells caused by the insertion of a transgene construct into the genetic locus for the basic leucine zipper transcription factor ATF-2. NK cells in this mouse were both phenotypically and functionally immature and accumulated in the bone marrow at a stage at which constitutive NK cell proliferation occurs in wild-type mice. Objective: We hypothesized that excess IL-15 could potentially overcome this developmental block, allowing normal emigration of mature NK cells from the bone marrow to the periphery. Methods: Double-transgenic mice were generated by crossing the NKD mice with transgenic mice overexpressing IL-15. Results: The double-transgenic mice had a dramatic accumulation of phenotypically immature NK cells in the bone marrow and subsequently in the blood, liver, and spleen. NK cells from these double-transgenic mice manifested functional deficits similar to those observed in NK cells from NKD mice, as assessed by decreased cytokine production and cytotoxicity. Conclusion: Rather than bypass the observed developmental defect in NKD mice, excess IL-15 drove a massive accumulation of phenotypically and functionally immature NK cells in the bone marrow and periphery. Clinical implications: We propose that these double-transgenic mice will serve as a murine model of chronic NK cell lymphocytosis in human patients.

Original languageEnglish
Pages (from-to)924-931
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number4
DOIs
StatePublished - Oct 1 2007

Keywords

  • CD11b
  • IL-15
  • Mac1
  • Natural killer cells
  • chronic natural killer cell lymphocytosis
  • lymphocytosis
  • natural killer cell-deficient mice

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