Development and analysis of natural killer cell-deficient mice.
Item
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Title
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Development and analysis of natural killer cell-deficient mice.
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Identifier
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AAI9917665
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identifier
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9917665
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Creator
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Kim, Sungjin.
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Contributor
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Adviser: Wayne M. Yokoyama
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Cell | Health Sciences, Immunology | Health Sciences, Oncology | Health Sciences, Pathology
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Abstract
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Since natural killer (NK) cells were discovered two decades ago, it has not been possible to directly demonstrate the physiological role of NK cells in immune responses because of the lack of available animal model with a selective loss of NK cell activity. The present study describes transgenic (Tg) mice that express an inhibitory MHC class I receptor Ly-49A under control of the mouse granzyme A promoter. Splenocytes from the Tg mice fail to kill various tumor targets in vitro but this defect is not due to the action of Ly-49A as an inhibitory receptor. Instead, there is a remarkable decrease in the number of CD3- NK1.1+ cells in peripheral organs. However, Tg mice possess a normal number of functional T, NK/T and B cells. Acute tumor rejection is impaired in Tg mice and can be reconstituted by the infusion of scid splenocytes. Taken together, these data demonstrate that Tg mice have a selective deficiency in the NK cell compartment. Studies of Tg mice also provide compelling evidence that NK cells are the major effector cells responsible for prevention of tumor metastasis, control of tumor outgrowth, acute rejection of beta2m-deficient bone marrow (BM) grafts, and acute production of IFN-gamma in response to bacterial endotoxin. In contrast to the peripheral organs, there is a significant increase in the number of CD3- NK1.1+ cells in the BM of Tg mice, suggesting a defect in the maturation process. CD3- NK1.1+ cells in Tg mice display a cell surface phenotype associated with immature NK cells. BM chimeric studies indicate that Tg mice have an intrinsic defect in the NK cell lineage with an intact microenvironment that can support normal NK cell maturation. Thus, this study also provides novel insights into the maturation process of NK cells.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
