Models to Study NK Cell Biology and Possible Clinical Application

Anthony E. Zamora1, Steven K. Grossenbacher1, Ethan G. Aguilar1, William J. Murphy2

1 Department of Dermatology, University of California, Davis, Sacramento, California, 2 Department of Internal Medicine, University of California, Davis, Sacramento, California
Publication Name:  Current Protocols in Immunology
Unit Number:  Unit 14.37
DOI:  10.1002/0471142735.im1437s110
Online Posting Date:  August, 2015
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Natural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. NK cells rapidly recognize and respond to abnormal cells in the absence of prior sensitization due to their wide array of germline‐encoded inhibitory and activating receptors, which differs from the receptor diversity found in B and T lymphocytes that is due to the use of recombination‐activation gene (RAG) enzymes. Although NK cells have traditionally been described as natural killers that provide a first line of defense prior to the induction of adaptive immunity, a more complex view of NK cells is beginning to emerge, indicating they may also function in various immunoregulatory roles and have the capacity to shape adaptive immune responses. With the growing appreciation for the diverse functions of NK cells, and recent technological advancements that allow for a more in‐depth understanding of NK cell biology, we can now begin to explore new ways to manipulate NK cells to increase their clinical utility. In this overview unit, we introduce the reader to various aspects of NK cell biology by reviewing topics ranging from NK cell diversity and function, mouse models, and the roles of NK cells in health and disease, to potential clinical applications. © 2015 by John Wiley & Sons, Inc.

Keywords: NK cell biology; mouse models; clinical application; natural killer cells

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • NK Cell Development
  • Human and Mouse NK Receptors
  • NK Cell Subsets
  • Functional Characteristics of NK Cells
  • Mouse Models of NK Cell Biology
  • NK Cells in Health and Disease
  • Concluding Remarks
  • Acknowledgements
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
  Biron, C.A., Nguyen, K.B., Pien, G.C., Cousens, L.P., and Salazar‐Mather, T.P. 1999. Natural killer cells in antiviral defense: Function and regulation by innate cytokines. Annu. Rev. Immunol.17:189‐220.
  Boissel, L., Betancur‐Boissel, M., Lu, W., Krause, D.S., Van Etten, R.A., Wels, W.S., and Klingemann, H. 2013. Retargeting NK‐92 cells by means of CD19‐ and CD20‐specific chimeric antigen receptors compares favorably with antibody‐dependent cellular cytotoxicity. Oncoimmunology 2:e26527.
  Brandt, E.J., Elliott, R.W., and Swank, R.T. 1975. Defective lysosomal enzyme secretion in kidneys of Chediak‐Higashi (beige) mice. J. Cell Biol. 67:774‐788.
  Cichocki, F., Sitnicka, E., and Bryceson, Y.T. 2014. NK cell development and function–plasticity and redundancy unleashed. Semin. Immunol. 26:114‐126.
  Cooper, M.A., Bush, J.E., Fehniger, T.A., VanDeusen, J.B., Waite, R.E., Liu, Y., Aguila, H.L., and Caligiuri, M.A. 2002. In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100:3633‐3638.
  Cudkowicz, G. and Bennett, M. 1971. Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice. J. Exp. Med. 134:1513‐1528.
  Dambrauskas, Z., Svensson, H., Joshi, M., Hyltander, A., Naredi, P., and Iresjo, B.M. 2014. Expression of major histocompatibility complex class I‐related chain A/B (MICA/B) in pancreatic carcinoma. Int. J. Oncol. 44:99‐104.
  Dillman, R.O., Duma, C.M., Schiltz, P.M., DePriest, C., Ellis, R.A., Okamoto, K., Beutel, L.D., De Leon, C., and Chico, S. 2004. Intracavitary placement of autologous lymphokine‐activated killer (LAK) cells after resection of recurrent glioblastoma. J. Immunother. 27:398‐404.
  Di Santo, J.P. 2006. Natural killer cell developmental pathways: A question of balance. Annu. Rev. Immunol. 24:257‐286.
  DiSanto, J.P., Muller, W., Guy‐Grand, D., Fischer, A., and Rajewsky, K. 1995. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc. Natl. Acad. Sci. U.S.A. 92:377‐381.
  Doubrovina, E.S., Doubrovin, M.M., Vider, E., Sisson, R.B., O'Reilly, R.J., Dupont, B., and Vyas, Y.M. 2003. Evasion from NK cell immunity by MHC class I chain‐related molecules expressing colon adenocarcinoma. J. Immunol. 171:6891‐6899.
  Hayakawa, Y., Huntington, N.D., Nutt, S.L., and Smyth, M.J. 2006. Functional subsets of mouse natural killer cells. Immunol. Rev. 214:47‐55.
  Herberman, R.B., Nunn, M.E., and Lavrin, D.H. 1975. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int. J. Cancer 16:216‐229.
  Hesslein, D.G. and Lanier, L.L. 2011. Transcriptional control of natural killer cell development and function. Adv. Immunol. 109:45‐85.
  Karre, K., Ljunggren, H.G., Piontek, G., and Kiessling, R. 1986. Selective rejection of H‐2‐deficient lymphoma variants suggests alternative immune defense strategy. Nature 319:675‐678.
  Kennedy, M.K., Glaccum, M., Brown, S.N., Butz, E.A., Viney, J.L., Embers, M., Matsuki, N., Charrier, K., Sedger, L., Willis, C.R., Brasel, K., Morrissey, P.J., Stocking, K., Schuh, J.C., Joyce, S., and Peschon, J.J. 2000. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15‐deficient mice. J. Exp. Med.191:771‐780.
  Kiessling, R., Klein, E., and Wigzell, H. 1975. “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur. J. Immunol. 5:112‐117.
  Kim, S., Poursine‐Laurent, J., Truscott, S.M., Lybarger, L., Song, Y.J., Yang, L., French, A.R., Sunwoo, J.B., Lemieux, S., Hansen, T.H., and Yokoyama, W.M. 2005. Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436:709‐713.
  Kohrt, H.E., Colevas, A.D., Houot, R., Weiskopf, K., Goldstein, M.J., Lund, P., Mueller, A., Sagiv‐Barfi, I., Marabelle, A., Lira, R., Troutner, E., Richards, L., Rajapaska, A., Hebb, J., Chester, C., Waller, E., Ostashko, A., Weng, W.K., Chen, L., Czerwinski, D., Fu, Y.X., Sunwoo, J., and Levy, R. 2014. Targeting CD137 enhances the efficacy of cetuximab. J. Clin. Invest. 124:2668‐2682.
  Kundig, T.M., Schorle, H., Bachmann, M.F., Hengartner, H., Zinkernagel, R.M., and Horak, I. 1993. Immune responses in interleukin‐2‐deficient mice. Science 262:1059‐1061.
  Lanier, L.L. 2008. Up on the tightrope: Natural killer cell activation and inhibition. Nat. Immunol. 9:495‐502.
  Lanier, L.L., Le, A.M., Phillips, J.H., Warner, N.L., and Babcock, G.F. 1983. Subpopulations of human natural killer cells defined by expression of the Leu‐7 (HNK‐1) and Leu‐11 (NK‐15) antigens. J. Immunol. 131:1789‐1796.
  Marquardt, N., Wilk, E., Pokoyski, C., Schmidt, R.E., and Jacobs, R. 2010. Murine CXCR3+CD27bright NK cells resemble the human CD56bright NK‐cell population. Eur. J. Immunol. 40:1428‐1439.
  Miller, J.S., Soignier, Y., Panoskaltsis‐Mortari, A., McNearney, S.A., Yun, G.H., Fautsch, S.K., McKenna, D., Le, C., Defor, T.E., Burns, L.J., Orchard, P.J., Blazar, B.R., Wagner, J.E., Slungaard, A., Weisdorf, D.J., Okazaki, I.J., and McGlave, P.B. 2005. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105:3051‐3057.
  Pegram, H.J., Andrews, D.M., Smyth, M.J., Darcy, P.K., and Kershaw, M.H. 2011. Activating and inhibitory receptors of natural killer cells. Immunol. Cell Biol. 89:216‐224.
  Raulet, D.H. and Vance, R.E. 2006. Self‐tolerance of natural killer cells. Nat. Rev. Immunol. 6:520‐531.
  Roder, J.C. 1979. The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function. J. Immunol. 123:2168‐2173.
  Rolle, A., Pollmann, J., and Cerwenka, A. 2013. Memory of infections: An emerging role for natural killer cells. PLoS Pathog. 9:e1003548.
  Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W.D., Tosti, A., Posati, S., Rogaia, D., Frassoni, F., Aversa, F., Martelli, M.F., and Velardi, A. 2002. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097‐2100.
  Shifrin, N., Raulet, D.H., and Ardolino, M. 2014. NK cell self tolerance, responsiveness and missing self recognition. Semin. Immunol. 26:138‐144.
  Small, T.N., Papadopoulos, E.B., Boulad, F., Black, P., Castro‐Malaspina, H., Childs, B.H., Collins, N., Gillio, A., George, D., Jakubowski, A., Heller, G., Fazzari, M., Kernan, N., MacKinnon, S., Szabolcs, P., Young, J.W., and O'Reilly, R.J. 1999. Comparison of immune reconstitution after unrelated and related T‐cell‐depleted bone marrow transplantation: Effect of patient age and donor leukocyte infusions. Blood 93:467‐480.
  Sun, J.C. and Lanier, L.L. 2011. NK cell development, homeostasis and function: Parallels with CD8(+) T cells. Nat. Rev. Immunol. 11:645‐657.
  Suzuki, H., Duncan, G.S., Takimoto, H., and Mak, T.W. 1997. Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL‐2 receptor beta chain. J. Exp. Med. 185:499‐505.
  Tian, Z.G. and Zhang, C. 2010. The Regulatory Natural Killer Cells. In Natural Killer Cells: At the Forefront of Modern Immunology (J. Zimmer, ed.) pp. 369‐389. Springer‐Verlag, New York and Heidelberg.
  Venstrom, J.M., Zheng, J., Noor, N., Danis, K.E., Yeh, A.W., Cheung, I.Y., Dupont, B., O'Reilly, R.J., Cheung, N.K., and Hsu, K.C. 2009. KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high‐risk neuroblastoma. Clin. Cancer Res. 15:7330‐7334.
  Wang, B., Wang, Q., Wang, Z., Jiang, J., Yu, S.C., Ping, Y.F., Yang, J., Xu, S.L., Ye, X.Z., Xu, C., Yang, L., Qian, C., Wang, J.M., Cui, Y.H., Zhang, X., and Bian, X.W. 2014. Metastatic consequences of immune escape from NK cell cytotoxicity by human breast cancer stem cells. Cancer Res. 74:5746‐5757.
  Zamai, L., Ahmad, M., Bennett, I.M., Azzoni, L., Alnemri, E.S., and Perussia, B. 1998. Natural killer (NK) cell‐mediated cytotoxicity: Differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J. Exp. Med. 188:2375‐2380.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library