Natural killer (NK) cells act as an important defense against malignancy through their ability to inhibit tumor metastases and destroy solid tumors and hematopoietic tumors. In addition natural killer cells have anti-microbial activity, giving them a role in combating infectious diseases caused by bacteria, fungi, yeast and protozoal parasites. NK cells also target and kill cells that are infected with various types of viruses including herpes, influenza, hepatitis, pox and orthomyxovirus. The inherent cytotoxicity of NK cells can be significantly enhanced by interaction of the NK cells with various cytokines and interferon via receptor-specific interactions. Such agents also induce the production of interferon-gamma by NK cells. A human natural killer cell line, NK 3.3, was established from soft agarose cloning of primary MLC activated cells in a medium containing interleukin-2. NK 3.3 cells mediate strong and exclusive natural killer cell activity and lack the pan T-cell marker as well as markers associated with T-cell subsets. Morphologic, histochemical and phenotypic characterizations showed that the NK 3.3 cell line is similar to members of the large granular lymphocyte population that contains the bulk of the NK cell population. NK 3.3 cells are CD3-, CD4-, CD8-, CD2+, CD16+, CD56+. They are capable of strong NK cell lysis of sensitive target cells. NK 3.3 cells have been shown to kill by both perforin/granzyme mediated granule exocytosis and by Fas-mediated killing. In addition, through their expression of the Fc receptor CD16, NK 3.3 cells mediate antibody dependent cellular cytotoxicity (ADCC). When activated by cytokines, such as IL-2 or interferons IL-12 or IL-15, NK 3.3 cells secrete interferon-gamma.The human natural killer cell line, NK 3.3, is useful screening target for assessing the potential of therapeutic drug candidates to increase or decrease NK cell cytolytic function and for their ability to modulate the level of production of interferon-gamma production.
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