Chronic lymphocytosis of functionally immature natural killer cells.

Chronic lymphocytosis of functionally immature natural killer cells. Research Abstract Details 

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Chronic lymphocytosis of functionally immature natural killer cells. Abstract Text:

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

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.

Chronic lymphocytosis of functionally immature natural killer cells. Publishing Authors By Initials

AR French,S Kim,TA Fehniger,JR Pratt,L Yang,YJ Song,MA Caligiuri,WM Yokoyama,AR French,S Kim,TA Fehniger,JR Pratt,L Yang,YJ Song,MA Caligiuri,WM Yokoyama,

For similar animals: animal population groups: organisms, genetically modified: animals, genetically modified: mice, transgenic research abstracts see: animals: animal population groups: organisms, genetically modified: animals, genetically modified: mice, transgenic research

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Chronic lymphocytosis of functionally immature natural killer cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of allergy and clinical immunology

VOLUME: 120

Page Numbers: 924-31

Journal Abbreviation: J. Allergy Clin. Immunol.

ISSN: 0091-6749

DAY: 2

MONTH: 07

YEAR: 2007

Chronic lymphocytosis of functionally immature natural killer cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 1275002

Chronic lymphocytosis of functionally immature natural killer cells. Keywords Mesh Terms:

KEYWORDS: Mice, Transgenic

MESH TERMS: etiology

Chemical & Substance for Abstract: Chronic lymphocytosis of functionally immature natural killer cells. Information

Substance Name: Interleukin-15

Registry Number: 0

Grant and Affiliation Information for Chronic lymphocytosis of functionally immature natural killer cells.

AFFILIATION: Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA. french_a@kids.wustl.edu

Country: United States

AGENCY: United States PHS

GRANT: K08

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MEDLINETA: J Allergy Clin Immunol

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