Abstract
Natural killer (NK) cells are a distinct compartment of lymphoid cells that have been shown to function as an effector cell population against virus infections, to provide a means of surveillance against tumor metastases, and, in some cases, to serve as an effector cell population for immunotherapy against established tumors. Since the initial observations suggesting that NK cells were representative of an “activity” expressed by some hematopoietic cells, as opposed to a defineable lineage of cells, an extraordinary increase in our capacity to identify, quantitate, and characterize these cells has occurred. This has been particularly apparent in the past several years, as numerous reagents for defining NK cell heterogeneity and function have been developed. There has also been a dramatic increase in the technology available for application of those reagents. NK cells have commonly been defined as a population of large granular lymphocytes (LGLs) that have a discrete phenotype, frequently defined as CD3-/TCR-/CD16+/CD56+, and that are capable of lysing certain tumor cells and virus-infected cells in the absence of any apparent, prior sensitization. NK cells also by definition lack expression of the TCR/CD3 complex and can be stimulated to lyse target cells utilizing surface receptors that do not detect specific antigen in the context of major histocompatibility complex (MHC) class I determinants. These findings initially led to their designation as mediators of non-MHC restricted cytotoxicity. It is now clear that MHC determinants are in fact recognized by NK cell surface receptors. Further, it has been determined that most such receptor-MHC interactions result in a turnoff of NK cells, although there are some exceptions in which receptor-MHC interactions activate NK cell lytic function (for recent reviews see refs. 1 and 2).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Moretta L., Ciccone E., Poggi A., Mingari M. C., and Moretta A. (1994) Ontogeny, specific functions and receptors of human natural killer cells. Immunol. Lett. 40, 83–88.
Lanier L. L. (1998) Follow the leader: NK cell receptors for classical and non-classical MHC class I. Cell 92, 705–707.
Eischen C. M., and Leibson P. J. (1997) Role for NK-cell-associated Fas ligand in cell-mediated cytotoxicity and apoptosis. Res. Immunol. 148, 164–169.
Gunji Y., Vujanovic N. L., Hiserodt J. C., Herberman R. B. and Gorelik E. (1989) Generation and characterization of purified adherent lymphokine-activated killer cells in mice. J. Immunol. 142, 1748–1754
Vujanovic N. L., Herberman R. B., Al Maghazachi A., and Hiserodt J. C. (1988) Lymphokine-activated killer cells in rats. III. A simple method for the purification of large granular lymphocytes and their rapid expansion and conversion into lymphokine-activated killer cells. J. Exp. Med. 167, 15–25.
Einspahr K. J., Abraham R. T., Dick C. J., and Leibson P. J. (1990) Protein tyrosine phosphorylation and p56lck modification in IL-2 or phorbol ester-activated human natural killer cells. J. Immunol. 145, 1490–1497.
Hori T., Phillips J. H., Duncan B., Lanier L. L., and Spits H. (1992) Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma, delta, and epsilon and proliferate in response to IL-2, IL-3, IL-4 or IL-7: implications for the relationship between T and natural killer cells. Blood 80, 1270–1278.
Brissette-Storkus C. S., Appasamy P. M., Hayes L. A., Kaufman C. L., Ildstad S. T., and Chambers W. H. (1995) Characterization and comparison of the lytic function of NKR-P1+ and NKR-P1- rat natural killer cell clones derived from NKR-P1bright/TCRaβ-cell lines. Nat. Immun. 14, 98–113.
Karlhofer F. M., Orihuela M. M., and Yokoyama W. M. (1995) Ly-49-indepen-dent natural killer (NK) cell specificity revealed by NK cell clones derived from p53-deficient mice. J. Exp. Med. 181, 1785–1795.
Manoussaka M. S., Smith R. J., Conlin V., Toomey J. A., and Brooks C. G. (1998) Fetal mouse NK cell clones are deficient in Ly49 expression, share a common broad lytic specificity, and undergo continuous and extensive diversification in vitro. J. Immunol. 160, 2197–2206.
Rabinowich H., Sedlmayr P., Herberman R. B., and Whiteside T. L. (1991) Increased proliferation, lytic activity, and purity of human natural killer cells co-cultured with mitogen-activated feeder cells. Cell. Immunol. 35, 454–470.
Melder R. J., Rosenfeld C. S., Herberman R. B., and Whiteside T. L. (1989) Large-scale preparation of adherent lymphokine-activated killer (A-LAK) cells for adoptive immunotherapy in man. Cancer Immunol. Immunother. 29, 67–73.
Melder R. J., Whiteside T. L., Vujanovic N. L., Hiserodt J. C., and Herberman R. B. (1988) A new approach to generating antitumor effectors for adoptive immunotherapy using human adherent lymphokine-activated killer cells. Cancer Res. 48, 3461–3469.
Chambers W. H., Vujanovic N. L., DeLeo A. B., Olszowy M. W., Herberman R. B., and Hiserodt. J. C. (1989) Monoclonal antibody to a triggering structure expressed on rat natural killer (NK) cells and adherent lymphokine activated killer (A-LAK) cells. J. Exp. Med. 169, 1373–1389.
Sentman C. L., Hackett J., Moore T. A., Tutt M. M., Bennett M., and Kumar V. (1989) Pan natural killer cell monoclonal antibodies and their relationship to the NK1. 1 antigen. Hybridoma 8, 605–614.
Garni-Wagner B. A., Purohit A., Mathew P. A., Bennett M., and Kumar V. (1993) A novel function-associated molecule related to non-MHC-restricted cytotoxicity mediated by activated natural killer cells and T cells. J. Immunol. 151, 60–70.
Lanier L. L., Chang C., Azuma M., Ruitenberg J. J., Hemperly J. J., and Phillips J. H. (1991) Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J. Immunol. 146, 4421–4426.
Lea R. G., McIntyre S., Baird J. D., and Clark D. A. (1998) Tumor necrosis factor-alpha mRNA-positive cells in spontaneous resorption in rodents. Am. J. Reprod. Immunol. 39, 50–57.
Ye W., Zheng L. M., Young J. D., and Liu C. C. (1996) Then involvement of interleukin (IL)-15 in regulating the differentiation of granulated metrial gland cells in mouse pregnant uterus. J. Exp. Med. 84, 2405–2410.
Salazar-Mather T. P., Ishikawa R., and Biron C. A. (1996) NK cell trafficking and cytokine expression in splenic compartments after IFN induction and viral infection. J. Immunol. 157, 3054–3064.
Parr E. L., Chen H. L., Parr M. B., and Hunt J. S. (1995.) Synthesis and granular localization of tumor necrosis factor-alpha in activated NK cells in the pregnant mouse uterus. J. Reprod. Immunol. 28, 31–40.
Chambers W. H., Bozik M. E., Brissette-Storkus C. S., Basse P. H., Redgate E., Watkins S. C., and Boggs S. S. (1996) NKR-P1+ Cells selectively localize in rat 9L gliosarcomas, but have reduced cytolytic function. Cancer Res. 56, 3516–3525.
Rosenberg S. A., Grimm E. A., McGrogan M., Doyle M., Kawasaki E., Koths K., and Mark D. F. (1984) Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science 223, 1412–1414.
Wang A., Lu S. D., and Mark D. F. (1984) Site-specific mutagenesis of the human interleukin-2 gene: Structure-function analyses of the cysteine residues. Science 224, 1431–1433.
Vujanovic N. L., Rabinowich H., Lee Y. J., Jost L., and Herberman R. B. (1993) Distinct phenotypic and functional characteristics of human natural killer cells obtained by rapid interleukin 2-induced adherence to plastic. Cell. Immunol. 139, 151–157.
Basse P. H., Herberman R. B., Nannmark U., Johansson B. R., Hokland M., Wasserman K., and Goldfarb R. H. (1991) Accumulation of Adoptively Transferred A-LAK Cells in Murine Metastases. J. Exp. Med. 174, 479–488.
Basse P. H., Nannmark U., Johansson B. R., Herberman R. B., and Goldfarb R. H. (1991) Establishment of cell-to-cell contact by adoptively transferred adherent lymphokine-activated killer cells with metastatic murine melanoma cells. J. Natl. Cancer Inst. 83, 944–950.
Basse P. H., Herberman R. B., Hokland M. E., and Goldfarb R. H. (1992) Tissue distribution of adoptively transferred adherent lymphokine-activated killer cells assessed by different cell labels. Cancer Immunol. Immunother. 34, 221–227.
Basse P. H., Herberman R. B., Hokland M. E., and Goldfarb R. H. (1992) Tissue distribution of adoptively transferred adherent lymphokine-activated killer cells: role of route of administration. Nat. Immunity Cell Growth Reg. 11, 193–202.
Kuppen P. J. K., Basse P. H., Goldfarb R. H., van der Velde C. J. H., Fleuren G. J., and Eggermont A. M. M. (1993) The infiltration of experimentally induced lung metastases of colon carcinoma CC531 by adoptively transferred interleukin-2-activated natural killer cells in Wag rats. Int. J. Cancer 56, 574–579.
Basse P. H., Goldfarb R. H., Herberman R. B., and Hokland M. E. (1994) Accumulation of adoptively transferred A-NK cells in murine metastases: kinetics and role of interleukin-2. In Vivo 8, 17–24.
Fidler I. J. (1970) Metastasis: Quantitative analysis of distribution and fate of tumor emboli labeled with 125I-5-Iodo-2’-deoxyuridine. J. Natl. Cancer. Inst. 45, 773–775.
Basse P. H., Hokland P., and Hokland M. E. (1990) Comparison between 125IUdR and 51Cr as cell labels in investigations of tumor cell migration. Nucl. Med.Biol. 17, 781–787.
Butcher E. C. and Weissman E. L. (1980) Direct fluorescent labeling of cells with fluorescein or rhodamine isothiocyanate. 1. Technical aspects. J. Immunol. Meth. 37, 97–104.
Butcher E. C. and Weissman E. L. (1980) Direct fluorescent labeling of cells with fluorescein or rhodamine isothiocyanate. II. Potential application to studies of lymphocyte migration and maturation. J. Immunol. Meth. 37, 109–114.
Olszewski W. L. (1987). In Vivo Migration of Immune Cells. CRC Press Boca Raton, Florida.
Basse P. H., Hokland P., Gundersen H. J. G., and Hokland M. (1992) Enumeration of organ-associated NK cells in mice; application of a new stereological method. APMIS 100, 202–20
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Humana Press Inc.
About this protocol
Cite this protocol
Chambers, W.H., Watkins, S.M., Basse, P.H. (1999). Methods for In Vivo Analyses of Natural Killer (NK) Cells. In: Campbell, K.S., Colonna, M. (eds) Natural Killer Cell Protocols. Methods in Molecular Biology, vol 121. Humana Press. https://doi.org/10.1385/1-59259-044-6:95
Download citation
DOI: https://doi.org/10.1385/1-59259-044-6:95
Publisher Name: Humana Press
Print ISBN: 978-0-89603-683-3
Online ISBN: 978-1-59259-044-5
eBook Packages: Springer Protocols