<i>In vivo</i>natural killer cell activities revealed by natural killer cell-deficient mice

Kim, Sung Jin; Iizuka, Kinji; Aguila, Héctor L.; Weissman, Irving L.; Yokoyama, Wayne M.

doi:10.1073/pnas.050588297

Cited by 390 publications

(302 citation statements)

References 47 publications

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“…NK cells mediate their effects through cellular cytotoxicity alongside the production of a range of cytokines and other immunoregulatory mediators (14)(15)(16)(17)(18)(19). Early resistance to intracellular pathogens, including M. tuberculosis, can be driven by IFN-g production and lysis of infected cells and through modulatory effects on T regulatory responses (20)(21)(22).…”

mentioning

confidence: 99%

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Hall

Clare

Dougan

2010

The Journal of Immunology

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mentioning

confidence: 99%

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Hall

Clare

Dougan

2010

The Journal of Immunology

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“…3 demonstrates that the levels of CD11b after IL-2 activation remained higher and were not reduced in the case of PLC␥2 Ϫ/Ϫ compared with that of WT. The majority of the developing NK1.1 ϩ CD3 Ϫ cells have been shown to express the integrin ␣ v (CD51) in the BM (34). However, the levels of CD51 have been reported to be down-regulated during NK cell maturation (20).…”

Section: Il-2 and Il-15 Cytokines Fail To Rescue The Developmental Dementioning

confidence: 99%

“…1C) with Abs against phenotypic markers such as CD122, NKG2D, NKG2A/C/E, CD51, CD49b, CD11b, CD43, and CD69 that are defined to reflect different developmental or functional stages of NK cells (17,34). The single CD3 ϩ (T cells) or the double NK1.1 ϩ CD3 ϩ (NKT) ϩ cells were excluded from these analyses.…”

Section: Lack Of Plc␥2 ϫ/ϫ Affects the Development Of Nk Cellsmentioning

confidence: 99%

Differential and Nonredundant Roles of Phospholipase Cγ2 and Phospholipase Cγ1 in the Terminal Maturation of NK Cells

Regunathan

Chen

Kutlesa

et al. 2006

The Journal of Immunology

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NK cells play a central role in mediating innate immune responses. Activation of NK cells results in cytotoxicity, cytokine, and chemokine secretions. In this study, we show that in mice with targeted deletion of phospholipase Cγ (PLCγ)2, one of the key signal transducers, there are profound effects on the development and terminal maturation of NK cells. Lack of PLCγ2 significantly impaired the ability of lineage-committed NK precursor cells to acquire subset-specific Ly49 receptors and thereby terminal maturation of NK cells. Overexpression of isozyme, PLCγ1, in PLCγ2-deficient NK cells resulted in the successful Ly49 acquisition and terminal maturation of the NK cells; however, it could only partially rescue NKG2D-mediated cytotoxicity with no cytokine production. Furthermore, PLCγ2-deficient NK cells failed to mediate antitumor cytotoxicity and inflammatory cytokine production, displaying a generalized hyporesponsiveness. Our results strongly demonstrate that PLCγ1 and PLCγ2 play nonredundant and obligatory roles in NK cell ontogeny and in its effector functions.

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“…Evidence gathered from a mouse xenograft tumor model testing functionally deficient NK cells or antibody-mediated NK cell depletion supports that NK cells can eradicate tumor cells. [38][39][40][41] An 11-year follow-up study in patients indicated that low NK-like cytotoxicity was associated with increased cancer risk. 42 High levels of tumor infiltrating NK cells (TINKs) are associated with a favorable tumor outcome in patients with colorectal carcinoma, gastric carcinoma and squamous cell lung cancer, suggesting that NK-cell infiltration into tumor tissues represents a positive prognostic marker.…”

Section: Conception Of Nk Cellsmentioning

confidence: 99%

NK cell-based immunotherapy for malignant diseases

et al. 2013

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Natural killer (NK) cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells (iPSCs), and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice (GMP) facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

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In vivonatural killer cell activities revealed by natural killer cell-deficient mice

Cited by 390 publications

References 47 publications

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Differential and Nonredundant Roles of Phospholipase Cγ2 and Phospholipase Cγ1 in the Terminal Maturation of NK Cells

NK cell-based immunotherapy for malignant diseases

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