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98-013 - Human natural killer (NK) 3.3 cell line

Researchers

Jacki Kornbluth

Summary

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.

Publications and References

Kornbluth J, Flomenberg N, and Dupont B:  Cell surface phenotype of a cloned line of human natural killer cells.  J. Immunol. 129:2831-2837, 1982.

Kornbluth J and Wilson DB:  Monoclonal antibodies directed against HLA molecules affect the lytic and proliferative behavior of a cloned line of human natural killer cells.  Human Immunol. 11:239-247, 1984.

Kornbluth J, Spear B, Raab SS, and Wilson DB:  Evidence for the role of class I and class II HLA antigens in the lytic function of a cloned line of human natural killer cells.  J. Immunol. 134:728-735, 1985.

Kornbluth J:  Human natural killer cells and cytotoxic T-lymphocytes require cell surface carbohydrate determinants for lytic function.  Cell. Immunol. 95:276-287, 1985.

Taylor DS, Nowell PC, and Kornbluth J:  Functional role of HLA class I cell surface molecules in human T lymphocyte activation and proliferation.  Proc. Natl. Acad. Sci. USA 83:4446-4450, 1986.

Hart MK, Kornbluth J, Main EK, Spear BT, Taylor DS, and Wilson DB:  Lymphocyte function-associated antigen 1 (LFA-1) and natural killer (NK) cell activity:  LFA-1 is not necessary for all killer: target cell interactions.  Cell. Immunol. 109:306-317, 1987.

Leiden JM, Gottesdiener KM, Quertermous T, Coury L, Bray RA, Gottschalk L, Seidman JG, Strominger JL, Landay AL, and Kornbluth J:  T cell receptor gene rearrangement in human natural killer cells:  Natural killer activity is not dependent upon the rearrangement and expression of T cell receptor alpha, beta, or gamma genes.  Immunogenetics 27:231-238, 1988.

Kornbluth J and Hoover RG:  Changes in gene expression associated with IFN-$ and IL-2 induced augmentation of human NK function.  J. Immunol. 141:3234-3240, 1988.

Mahle NH, Radcliff G, Sevilla CL, Kornbluth J, and Callewaert D:  Kinetics of cellular cytotoxicity mediated by a cloned human killer cell line.  Immunobiol.  179:230-243, 1989.

Kornbluth J and Hoover R:  Changes in gene expression associated with natural killer function.  In:  Natural Killer Cells and Host Defense.  E.W. Ades and C. Lopez, eds., S. Karger AG, Basel, p. 68-74, 1989.

Kornbluth J and Hoover RG:  Anti-HLA class I antibodies alter gene expression in human natural killer cells.  In: Immunobiology of HLA, Vol. 2, Immunogenetics and Histocompatibility, B. Dupont, ed., Springer-Verlag, New York, NY, p. 150-152, 1989.

Kornbluth J, and Searfoss L:  C-myb protooncogene levels correlate with interleukin-2 and interferon-$ induced augmentation of natural killer activity.  Natural Killer Cells: Biology and Clinical Applications.  S. Karger AG, Basel, p. 212-215, 1990.

Hayakawa K, Salmeron MA, Kornbluth J, Bucana C, and Itoh K:  The role of IL-4 in proliferation and differentiation of human natural killer cells.  Study of an IL-4 dependent versus an IL-2 dependent natural killer cell clone.  J. Immunol.  146:2453-2460, 1991.

Chehimi J, Bandyopadhyay B, Prakash K, Perussia B, Hassan NK, Kawashima H, Campbell D, Kornbluth J, and Starr SE:  In vitro infection of natural killer cells with different human immunodeficiency virus type 1 isolates.  J. Virology.  65:1812-1822, 1991.

Kozlowski M, Schorey J, Portis T, Grigoriev V and Kornbluth J: NKLAM: A novel gene selectively expressed in cells with cytolytic function. J. Immunol.163:1775-1785, 1999.

Portis T, Anderson J, Esposito A and Kornbluth J: Gene structure of human and murine NKLAM, a gene associated with cellular cytotoxicity. Immunogenetics 51:546-555, 2000.

Fortier J and Kornbluth J: NK Lytic-Associated Molecule, involved in NK cytolytic function, is an E3 ligase. J. Immunol. 176: 6454-6463, 2006.

Hoover RG, Gullickson G and Kornbluth J: Impaired NK cytolytic activity and enhanced tumor growth in NK Lytic-Associated Molecule (NKLAM)-deficient mice. J. Immunol. 183: 6913-69211, 2009.

Lawrence DW and Kornbluth J: E3 ubiquitin ligase NKLAM is a macrophage phagosome protein and plays a role in bacterial killing. Cell. Immunol. 279: 46-52, 2012. 

Hoover RG, Gullickson G and Kornbluth J: Natural killer lytic-associated molecule plays a role in controlling tumor dissemination and metastasis. Frontiers Immunol. 3 (393): 1-9, 2012.

Bhattacharya S, Muhammad N, Steele R, Kornbluth J, Ray RB: Bitter melon enhances natural killer-mediated toxicity against head and neck cancer cells. Cancer Prev. Res. 10 (6):1-7, 2017.

Intellectual Property Status

  • Non-patented intellectual property