Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Development of Natural Killer Cells from Hematopoietic Stem Cells

  • Yoon, Suk Ran (Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Chung, Jin Woong (Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Choi, Inpyo (Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2007.06.27
  • Accepted : 2007.07.02
  • Published : 2007.08.31
⟨ Previous Next ⟩

Abstract

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

Keywords

Acknowledgement

Supported by : Ministry of Science and Technology

References

  1. Becknell, B. and Caligiuri, M. A. (2005) Interleukin-2, interleukin- 15, and their roles in human natural killer cells. Adv. Immunol. 86, 209-239 https://doi.org/10.1016/S0065-2776(04)86006-1
  2. Biron, C. A. (1998) Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections. Semin. Immunol. 10, 383-390
  3. Boggs, S. S., Trevisan, M., Patrene, K., and Geogopoulos, K. (1998) Lack of natural killer cell precursors in fetal liver of Ikaros knockout mutant mice. Nat. Immun. 16, 137-145 https://doi.org/10.1159/000069438
  4. Budagian, V., Bulanova, E., Paus, R., and Bulfone-Paus, S. (2006) IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev. 17, 259-280 https://doi.org/10.1016/j.cytogfr.2006.05.001
  5. Carson, W. E., Giri, J. G., Lindemann, M. J., Linett, M. L., Ahdieh, M., et al. (1994) Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J. Exp. Med. 180, 1395-1403 https://doi.org/10.1084/jem.180.4.1395
  6. Colonna, M. (1997) Immunoglobulin superfamily inhibitory receptors: from natural killer cells to antigen-presenting cells. Res. Immunol. 148, 169-171
  7. Colonna, M. and Samaridis, J. (1995) Cloning of immunoglobulin- superfamily members associated with HLA-C and HLAB recognition by human natural killer cells. Science (New York, N.Y) 268, 405-408 https://doi.org/10.1126/science.7716543
  8. Cosman, D., Mullberg, J., Sutherland, C. L., Chin, W., Armitage, R., et al. (2001) ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14, 123-133 https://doi.org/10.1016/S1074-7613(01)00084-X
  9. Di Santo, J. P. (2006) Natural killer cell developmental pathways: a question of balance. Annu. Rev. Immunol. 24, 257-286 https://doi.org/10.1146/annurev.immunol.24.021605.090700
  10. Dorfman, J. R. and Raulet, D. H. (1998) Acquisition of Ly49 receptor expression by developing natural killer cells. J. Exp. Med. 187, 609-618 https://doi.org/10.1084/jem.187.4.609
  11. Draghi, M., Yawata, N., Gleimer, M., Yawata, M., Valiante, N. M., et al. (2005) Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I. Blood 105, 2028-2035 https://doi.org/10.1182/blood-2004-08-3174
  12. Farag, S. S. and Caligiuri, M. A. (2004) Cytokine modulation of the innate immune system in the treatment of leukemia and lymphoma. Adv. Pharmacol. (San Diego, Calif) 51, 295-318 https://doi.org/10.1016/S1054-3589(04)51001-3
  13. Farag, S. S. and Caligiuri, M. A. (2006) Human natural killer cell development and biology. Blood Rev. 20, 123-137 https://doi.org/10.1016/j.blre.2005.10.001
  14. Farag, S. S., Fehniger, T. A., Ruggeri, L., Velardi, A., and Caligiuri, M. A. (2002) Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood 100, 1935-1947 https://doi.org/10.1182/blood-2002-02-0350
  15. Ferlazzo, G., Thomas, D., Lin, S. L., Goodman, K., Morandi, B., et al. (2004) The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Iglike receptors and become cytolytic. J. Immunol. 172, 1455-1462 https://doi.org/10.4049/jimmunol.172.3.1455
  16. Fernandez, N. C., Treiner, E., Vance, R. E., Jamieson, A. M., Lemieux, S., et al. (2005) A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105, 4416-4423 https://doi.org/10.1182/blood-2004-08-3156
  17. Freud, A. G. and Caligiur, M. A. (2006) Human natural killer cell development. Immunol. Rev. 214, 56-72 https://doi.org/10.1111/j.1600-065X.2006.00451.x
  18. Giebel, S., Locatelli, F., Lamparelli, T., Velardi, A., Davies, S., et al. (2003) Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood 102, 814-819 https://doi.org/10.1182/blood-2003-01-0091
  19. Hayashi, T., Hideshima, T., Akiyama, M., Podar, K., Yasui, H., et al. (2005) Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br. J. Haematol. 128, 192-203 https://doi.org/10.1111/j.1365-2141.2004.05286.x
  20. Held, W., Coudert, J. D., and Zimmer, J. (2003) The NK cell receptor repertoire: formation, adaptation and exploitation. Curr. Opin. Immunol. 15, 233-237 https://doi.org/10.1016/S0952-7915(02)00031-6
  21. Iizuka, K., Chaplin, D. D., Wang, Y., Wu, Q., Pegg, L. E., et al. (1999) Requirement for membrane lymphotoxin in natural killer cell development. Proc. Natl. Acad. Sci. USA 96, 6336-6340
  22. Ikawa, T., Fujimoto, S., Kawamoto, H., Katsura, Y., and Yokota, Y. (2001) Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc. Natl. Acad. Sci. USA 98, 5164-5169
  23. Kather, A., Chantakru, S., He, H., Minhas, K., Foster, R., et al. (2003) Neither lymphotoxin alpha nor lymphotoxin beta receptor expression is required for biogenesis of lymphoid aggregates or differentiation of natural killer cells in the pregnant mouse uterus. Immunology 108, 338-345 https://doi.org/10.1046/j.1365-2567.2003.01586.x
  24. Kim, S., Poursine-Laurent, J., Truscott, S. M., Lybarger, L., Song, Y. J., et al. (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436, 709-713 https://doi.org/10.1038/nature03847
  25. Klingemann, H. G. (2005) Natural killer cell-based immunotherapeutic strategies. Cytotherapy 7, 16-22 https://doi.org/10.1080/14653240510018000
  26. Krause, S. W., Gastpar, R., Andreesen, R., Gross, C., Ullrich, H., et al. (2004) Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial. Clin. Cancer Res. 10, 3699-3707 https://doi.org/10.1158/1078-0432.CCR-03-0683
  27. Lanier, L. L. (2001) Face off--the interplay between activating and inhibitory immune receptors. Curr. Opin. Immunol. 13, 326-331 https://doi.org/10.1016/S0952-7915(00)00172-2
  28. Lanier, L. L., Corliss, B. C., Wu, J., Leong, C., and Phillips, J. H. (1998) Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 391, 703-707 https://doi.org/10.1038/35642
  29. Lee, K. N., Kang, H. S., Jeon, J. H., Kim, E. M., Yoon, S. R., et al. (2005) VDUP1 is required for the development of natural killer cells. Immunity 22, 195-208 https://doi.org/10.1016/j.immuni.2004.12.012
  30. Lian, R. H., Chin, R. K., Nemeth, H. E., Libby, S. L., Fu, Y. X., et al. (2004) A role for lymphotoxin in the acquisition of Ly49 receptors during NK cell development. Eur. J. Immunol. 34, 2699-2707 https://doi.org/10.1002/eji.200425394
  31. Lian, R. H. and Kumar, V. (2002) Murine natural killer cell progenitors and their requirements for development. Semin. Immunol. 14, 453-460
  32. Link, B. K., Ballas, Z. K., Weisdorf, D., Wooldridge, J. E., Bossler, A. D., et al. (2006) Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin lymphoma. J. Immunother. (1997) 29, 558-568 https://doi.org/10.1097/01.cji.0000211304.60126.8f
  33. Ljunggren, H. G. and Karre, K. (1985) Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J. Exp. Med. 162, 1745-1759 https://doi.org/10.1084/jem.162.6.1745
  34. Ljunggren, H. G. and Karre, K. (1990) In search of the 'missing self': MHC molecules and NK cell recognition. Immunol. Today 11, 237-244 https://doi.org/10.1016/0167-5699(90)90002-Q
  35. Ljunggren, H. G. and Malmberg, K. J. (2007) Prospects for the use of NK cells in immunotherapy of human cancer. Nat. Rev. Immunol. 7, 329-339 https://doi.org/10.1038/nri2073
  36. Ljunggren, H. G., Ohlen, C., Hoglund, P., Yamasaki, T., Klein, G., et al. (1988) Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. J. Immunol. 140, 671-678
  37. Lohoff, M., Duncan, G. S., Ferrick, D., Mittrucker, H. W., Bischof, S., et al. (2000) Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells. J. Exp. Med. 192, 325-336 https://doi.org/10.1084/jem.192.1.1
  38. Maki, G., Klingemann, H. G., Martinson, J. A., and Tam, Y. K. (2001) Factors regulating the cytotoxic activity of the human natural killer cell line, NK-92. J. Hematother. Stem Cell Res. 10, 369-383
  39. Makrigiannis, A. P., Pau, A. T., Schwartzberg, P. L., McVicar, D. W., Beck, T. W., et al. (2002) A BAC contig map of the Ly49 gene cluster in 129 mice reveals extensive differences in gene content relative to C57BL/6 mice. Genomics 79, 437-444 https://doi.org/10.1006/geno.2002.6724
  40. Miller, J. S., Cooley, S., Parham, P., Farag, S. S., Verneris, M. R., et al. (2007) Missing KIR-ligands is associated with less relapse and increased graft versus host disease (GVHD) following unrelated donor allogeneic HCT. Blood 109, 5058-5061 https://doi.org/10.1182/blood-2006-10-051144
  41. Moretta, L. and Moretta, A. (2004) Killer immunoglobulin-like receptors. Curr. Opin. Immunol. 16, 626-633 https://doi.org/10.1016/j.coi.2004.07.010
  42. Moretta, A., Bottino, C., Sivori, S., Marcenaro, E., Castriconi, R., et al. (2001) Natural killer lymphocytes: 'null cells' no more. Ital. J. Anat. Embryol. 106, 335-342
  43. Mrozek, E., Anderson, P., and Caligiuri, M. A. (1996) Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood 87, 2632-2640
  44. Ogasawara, K., Hida, S., Azimi, N., Tagaya, Y., Sato, T., et al. (1998) Requirement for IRF-1 in the microenvironment supporting development of natural killer cells. Nature 391, 700-703 https://doi.org/10.1038/35636
  45. Passweg, J. R., Tichelli, A., Meyer-Monard, S., Heim, D., Stern, M., et al. (2004) Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia 18, 1835-1838 https://doi.org/10.1038/sj.leu.2403524
  46. Petersson, M. G., Gronberg, A., Kiessling, R., and Ferm, M. T. (1995) Engagement of MHC class I proteins on natural killer cells inhibits their killing capacity. Scandinavian J. Immunol. 42, 34-38 https://doi.org/10.1111/j.1365-3083.1995.tb03622.x
  47. Raulet, D. H., Held, W., Correa, I., Dorfman, J. R., Wu, M. F., et al. (1997) Specificity, tolerance and developmental regulation of natural killer cells defined by expression of class Ispecific Ly49 receptors. Immunol. Rev. 155, 41-52
  48. Raulet, D. H., Vance, R. E., and McMahon, C. W. (2001) Regulation of the natural killer cell receptor repertoire. Annu. Rev. Immunol. 19, 291-330 https://doi.org/10.1146/annurev.immunol.19.1.1
  49. Rosenberg, S. (1985) Lymphokine-activated killer cells: a new approach to immunotherapy of cancer. J. Natl. Cancer Inst. 75, 595-603
  50. Rosenberg, S. A. (2000) Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer. Cancer J. Sci. Am 6 (Suppl 1), S2-7
  51. Rosenberg, S. A., Lotze, M. T., Muul, L. M., Leitman, S., Chang, A. E., et al. (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N. Engl. J. Med. 313, 1485-1492
  52. Rosmaraki, E. E., Douagi, I., Roth, C., Colucci, F., Cumano, A., et al. (2001) Identification of committed NK cell progenitors in adult murine bone marrow. Eur. J. Immunol. 31, 1900-1909 https://doi.org/10.1002/1521-4141(200101)31:1<1::AID-IMMU1>3.0.CO;2-W
  53. Roth, C., Carlyle, J. R., Takizawa, H., and Raulet, D. H. (2000) Clonal acquisition of inhibitory Ly49 receptors on developing NK cells is successively restricted and regulated by stromal class I MHC. Immunity 13, 143-153 https://doi.org/10.1016/S1074-7613(00)00015-7
  54. Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W. D., et al. (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science (New York, N.Y) 295, 2097-2100 https://doi.org/10.1126/science.1068440
  55. Ruggeri, L., Mancusi, A., Burchielli, E., Aversa, F., Martelli, M. F., et al. (2006) Natural killer cell alloreactivity and haploidentical hematopoietic transplantation. Cytotherapy 8, 554-558 https://doi.org/10.1080/14653240601078721
  56. Ruggeri, L., Mancusi, A., Perruccio, K., Burchielli, E., Martelli, M. F., et al. (2005) Natural killer cell alloreactivity for leukemia therapy. J. Immunother. (1997) 28, 175-182 https://doi.org/10.1097/01.cji.0000161395.88959.1f
  57. Ryan, J. C. and Seaman, W. E. (1997) Divergent functions of lectin-like receptors on NK cells. Immunol. Rev. 155, 79-89 https://doi.org/10.1111/j.1600-065X.1997.tb00941.x
  58. Saito, S., Nishikawa, K., Morii, T., Enomoto, M., Narita, N., et al. (1993) Cytokine production by CD16-CD56bright natural killer cells in the human early pregnancy decidua. Int. Immunol. 5, 559-563 https://doi.org/10.1093/intimm/5.5.559
  59. Samson, S. I., Richard, O., Tavian, M., Ranson, T., Vosshenrich, C. A., et al. (2003) GATA-3 promotes maturation, IFNgamma production, and liver-specific homing of NK cells. Immunity 19, 701-711 https://doi.org/10.1016/S1074-7613(03)00180-8
  60. Shlomchik, W. D., Couzens, M. S., Tang, C. B., McNiff, J., Robert, M. E., et al. (1999) Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science (New York, N.Y) 285, 412-415 https://doi.org/10.1126/science.285.5426.412
  61. Singh, H., Medina, K. L., and Pongubala, J. M. (2005) Contingent gene regulatory networks and B cell fate specification. Proc. Natl. Acad. Sci. USA 102, 4949-4953
  62. Smyth, M. J., Cretney, E., Kershaw, M. H., and Hayakawa, Y. (2004) Cytokines in cancer immunity and immunotherapy. Immunol. Rev. 202, 275-293 https://doi.org/10.1111/j.0105-2896.2004.00199.x
  63. Suck, G. (2006) Novel approaches using natural killer cells in cancer therapy. Semin. Cancer Biol. 16, 412-418
  64. Taki, S., Nakajima, S., Ichikawa, E., Saito, T., and Hida, S. (2005) IFN regulatory factor-2 deficiency revealed a novel checkpoint critical for the generation of peripheral NK cells. J. Immunol. 174, 6005-6012 https://doi.org/10.4049/jimmunol.174.10.6005
  65. Tam, Y. K., Martinson, J. A., Doligosa, K., and Klingemann, H. G. (2003) Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice conditions for clinical adoptive cellular immunotherapy. Cytotherapy 5, 259-272 https://doi.org/10.1080/14653240310001523
  66. Townsend, M. J., Weinmann, A. S., Matsuda, J. L., Salomon, R., Farnham, P. J., et al. (2004) T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. Immunity 20, 477-494 https://doi.org/10.1016/S1074-7613(04)00076-7
  67. Trowsdale, J., Barten, R., Haude, A., Stewart, C. A., Beck, S., et al. (2001) The genomic context of natural killer receptor extended gene families. Immunol. Rev. 181, 20-38
  68. Uhrberg, M., Parham, P., and Wernet, P. (2002) Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes. Immunogenetics 54, 221-229 https://doi.org/10.1007/s00251-002-0429-9
  69. Uhrberg, M., Valiante, N. M., Shum, B. P., Shilling, H. G., Lienert-Weidenbach, K., et al. (1997) Human diversity in killer cell inhibitory receptor genes. Immunity 7, 753-763 https://doi.org/10.1016/S1074-7613(00)80394-5
  70. Valiante, N. M., Uhrberg, M., Shilling, H. G., Lienert- Weidenbach, K., Arnett, K. L., et al. (1997) Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity 7, 739-751 https://doi.org/10.1016/S1074-7613(00)80505-1
  71. van den Brink, M. R., Boggs, S. S., Herberman, R. B., and Hiserodt, J. C. (1990) The generation of natural killer (NK) cells from NK precursor cells in rat long-term bone marrow cultures. J. Exp. Med. 172, 303-313 https://doi.org/10.1084/jem.172.1.303
  72. Vance, R. E., Kraft, J. R., Altman, J. D., Jensen, P. E., and Raulet, D. H. (1998) Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b). J. Exp. Med. 188, 1841-1848 https://doi.org/10.1084/jem.188.1.1
  73. Vitale, M., Zimmer, J., Castriconi, R., Hanau, D., Donato, L., et al. (2002) Analysis of natural killer cells in TAP2-deficient patients: expression of functional triggering receptors and evidence for the existence of inhibitory receptor(s) that prevent lysis of normal autologous cells. Blood 99, 1723-1729 https://doi.org/10.1182/blood.V99.5.1723
  74. Vosshenrich, C. A., Ranson, T., Samson, S. I., Corcuff, E., Colucci, F., et al. (2005) Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J. Immunol. 174, 1213-1221 https://doi.org/10.4049/jimmunol.174.1.1
  75. Wagtmann, N., Rajagopalan, S., Winter, C. C., Peruzzi, M., and Long, E. O. (1995) Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. Immunity 3, 801-809 https://doi.org/10.1016/1074-7613(95)90152-3
  76. Warren, L. A. and Rothenberg, E. V. (2003) Regulatory coding of lymphoid lineage choice by hematopoietic transcription factors. Curr. Opin. Immunol. 15, 166-175 https://doi.org/10.1016/S0952-7915(03)00011-6
  77. Williams, N. S., Klem, J., Puzanov, I. J., Sivakumar, P. V., Bennett, M., et al. (1999) Differentiation of NK1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells. J. Immunol. 163, 2648-2656
  78. Williams, N. S., Kubota, A., Bennett, M., Kumar, V., and Takei, F. (2000) Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression. Eur. J. Immunol. 30, 2074-2082 https://doi.org/10.1002/1521-4141(200007)30:7<2074::AID-IMMU2074>3.0.CO;2-#
  79. Williams, N. S., Moore, T. A., Schatzle, J. D., Puzanov, I. J., Sivakumar, P. V., et al. (1997) Generation of lytic natural killer 1.1+, Ly-49- cells from multipotential murine bone marrow progenitors in a stroma-free culture: definition of cytokine requirements and developmental intermediates. J. Exp. Med. 186, 1609-1614 https://doi.org/10.1084/jem.186.1.1
  80. Yokoyama, W. M. (1995) Natural killer cell receptors. Curr. Opin. Immunol. 7, 110-120 https://doi.org/10.1016/0952-7915(95)80036-0
  81. Yokoyama, W. M. and Kim, S. (2006) Licensing of natural killer cells by self-major histocompatibility complex class I. Immunol. Rev. 214, 143-154 https://doi.org/10.1111/j.1600-065X.2006.00458.x