Chronic lymphocytosis of functionally immature natural killer cells

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:120

Article

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

关键词: natural killer cells;    lymphocytosis;    chronic natural killer cell lymphocytosis;    natural killer cell-deficient mice;    IL-15;    CD11b;    Mac1;   

DOI  :  10.1016/j.jaci.2007.05.022

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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