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Dissecting Human NK Cell Development and Differentiation

  • Nicholas D. Huntington
  • Jean-Jacques Mention
  • Christian Vosshenrich
  • Naoko Satoh-Takayama
  • James P. Di SantoEmail author
Chapter

Abstract

Our understanding of human NK cell biology lags behind that of the mouse NK cell biology; this is in a large part because of the ethical and logistical restrictions to the access of healthy human lymphoid tissue and the experimental manipulation in vivo. Nevertheless, in-depth analyses in genetically modified mice have provided us with models for NK cell development, differentiation, and function that guide our thinking about the role of NK cells in immune defense. Collectively, mouse and human studies have unveiled a number of conserved transcription factors, cytokines, cell surface receptors, and associated signaling proteins that are essential for normal NK cell development. Still, human and mouse NK cells differ with regard to expression of several key cell surface receptors, kinetics of development, and frequency in adult lymphoid organs (Huntington ND, Vosshenrich CA, Di Santo JP. Nat Rev Immunol 7:703–714, 2007). Accordingly, the specific biological roles for NK cells in human immune responses remain poorly described. New preclinical animal models that allow the analysis of human immune system development in function may provide a means to further our understanding of the biology of human NK cells in vivo.

Keywords

Haematopoietic Stem Cell Human Immune System Transporter Associate With Antigen Processing Lamina Propria Lymphocyte Lymphoid Tissue Inducer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work is supported by grants from Institut Pasteur, INSERM, Ligue Nationale contre le Cancer, Human Frontiers Science Program, National Health and Medical Research Council of Australia, and a Grand Challenges in Global Health grant from the Bill and Melinda Gates Foundation.

References

  1. 1.
    Blom B, Spits H (2006) Development of human lymphoid cells. Annu Rev Immunol 24: 287–320PubMedGoogle Scholar
  2. 2.
    Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, Wijnands E, Blom B, Spits H (2004) Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. Blood 104:3886–3893PubMedGoogle Scholar
  3. 3.
    Jaleco AC, Blom B, Res P, Weijer K, Lanier LL, Phillips JH, Spits H (1997) Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells. J Immunol 159:694–702PubMedGoogle Scholar
  4. 4.
    Spits H, Lanier LL, Phillips JH (1995) Development of human T and natural killer cells. Blood 85:2654–2670PubMedGoogle Scholar
  5. 5.
    Cobaleda C, Schebesta A, Delogu A, Busslinger M (2007) Pax5: the guardian of B cell identity and function. Nat Immunol 8:463–470PubMedGoogle Scholar
  6. 6.
    Laiosa CV, Stadtfeld M, Graf T (2006) Determinants of lymphoid-myeloid lineage diversification. Annu Rev Immunol 24:705–738PubMedGoogle Scholar
  7. 7.
    Maillard I, Fang T, Pear WS (2005) Regulation of lymphoid development, differentiation, and function by the Notch pathway. Annu Rev Immunol 23:945–974PubMedGoogle Scholar
  8. 8.
    Pear WS, Radtke F (2003) Notch signaling in lymphopoiesis. Semin Immunol 15:69–79PubMedGoogle Scholar
  9. 9.
    Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336PubMedGoogle Scholar
  10. 10.
    Boos MD, Yokota Y, Eberl G, Kee BL (2007) Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med 204:1119–1130PubMedGoogle Scholar
  11. 11.
    Ikawa T, Fujimoto S, Kawamoto H, Katsura Y, Yokota Y (2001) Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc Natl Acad Sci USA 98:5164–5169PubMedGoogle Scholar
  12. 12.
    Spits H, Couwenberg F, Bakker AQ, Weijer K, Uittenbogaart CH (2000) Id2 and Id3 inhibit development of CD34(+) stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. J Exp Med 192:1775–1784PubMedGoogle Scholar
  13. 13.
    Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P (1999) Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702–706PubMedGoogle Scholar
  14. 14.
    Heemskerk MH, Blom B, Nolan G, Stegmann AP, Bakker AQ, Weijer K, Res PC, Spits H (1997) Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3. J Exp Med 186:1597–1602PubMedGoogle Scholar
  15. 15.
    Lohoff M, Duncan GS, Ferrick D, Mittrucker HW, Bischof S, Prechtl S, Rollinghoff M, Schmitt E, Pahl A, Mak TW (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 192:325–336PubMedGoogle Scholar
  16. 16.
    Samson SI, Richard O, Tavian M, Ranson T, Vosshenrich CA, Colucci F, Buer J, Grosveld F, Godin I, Di Santo JP (2003) GATA-3 promotes maturation, IFN-gamma production, and liver-specific homing of NK cells. Immunity 19:701–711PubMedGoogle Scholar
  17. 17.
    Sunwoo JB, Kim S, Yang L, Naik T, Higuchi DA, Rubenstein JL, Yokoyama WM (2008) Distal-less homeobox transcription factors regulate development and maturation of natural killer cells. Proc Natl Acad Sci USA 105:10877–10882PubMedGoogle Scholar
  18. 18.
    Townsend MJ, Weinmann AS, Matsuda JL, Salomon R, Farnham PJ, Biron CA, Gapin L, Glimcher LH (2004) T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. Immunity 20:477–494PubMedGoogle Scholar
  19. 19.
    Ma A, Koka R, Burkett P (2006) Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 24:657–679PubMedGoogle Scholar
  20. 20.
    Rosmaraki EE, Douagi I, Roth C, Colucci F, Cumano A, Di Santo JP (2001) Identification of committed NK cell progenitors in adult murine bone marrow. Eur J Immunol 31:1900–1909PubMedGoogle Scholar
  21. 21.
    Rossi MI, Yokota T, Medina KL, Garrett KP, Comp PC, Schipul AH Jr, Kincade PW (2003) B lymphopoiesis is active throughout human life, but there are developmental age-related changes. Blood 101:576–584PubMedGoogle Scholar
  22. 22.
    McKenna HJ, Stocking KL, Miller RE, Brasel K, De Smedt T, Maraskovsky E, Maliszewski CR, Lynch DH, Smith J, Pulendran B et al (2000) Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95:3489–3497PubMedGoogle Scholar
  23. 23.
    Iizuka K, Chaplin DD, Wang Y, Wu Q, Pegg LE, Yokoyama WM, Fu YX (1999) Requirement for membrane lymphotoxin in natural killer cell development. Proc Natl Acad Sci USA 96:6336–6340PubMedGoogle Scholar
  24. 24.
    Chung JW, Kim MS, Piao ZH, Jeong M, Yoon SR, Shin N, Kim SY, Hwang ES, Yang Y, Lee YH et al (2008) Osteopontin promotes the development of natural killer cells from hematopoietic stem cells. Stem Cells 26:2114–2123PubMedGoogle Scholar
  25. 25.
    Huntington ND, Vosshenrich CA, Di Santo JP (2007) Developmental pathways that generate natural-killer-cell diversity in mice and humans. Nat Rev Immunol 7:703–714PubMedGoogle Scholar
  26. 26.
    Di Santo JP (2006) Natural killer cell developmental pathways: a question of balance. Annu Rev Immunol 24:257–286PubMedGoogle Scholar
  27. 27.
    Ranson T, Vosshenrich CA, Corcuff E, Richard O, Muller W, Di Santo JP (2003) IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood 101:4887–4893PubMedGoogle Scholar
  28. 28.
    Burkett PR, Koka R, Chien M, Chai S, Boone DL, Ma A (2004) Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. J Exp Med 200:825–834PubMedGoogle Scholar
  29. 29.
    Cooper MA, Bush JE, Fehniger TA, VanDeusen JB, Waite RE, Liu Y, Aguila HL, Caligiuri MA (2002) In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100:3633–3638PubMedGoogle Scholar
  30. 30.
    Dubois S, Mariner J, Waldmann TA, Tagaya Y (2002) IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells. Immunity 17:537–547PubMedGoogle Scholar
  31. 31.
    Koka R, Burkett PR, Chien M, Chai S, Chan F, Lodolce JP, Boone DL, Ma A (2003) Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice. J Exp Med 197:977–984PubMedGoogle Scholar
  32. 32.
    Sandau MM, Schluns KS, Lefrancois L, Jameson SC (2004) Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells. J Immunol 173:6537–6541PubMedGoogle Scholar
  33. 33.
    Mortier E, Woo T, Advincula R, Gozalo S, Ma A (2008) IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 205:1213–1225PubMedGoogle Scholar
  34. 34.
    Buckley RH (2004) Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol 22:625–655PubMedGoogle Scholar
  35. 35.
    Gilmour KC, Fujii H, Cranston T, Davies EG, Kinnon C, Gaspar HB (2001) Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency. Blood 98:877–879PubMedGoogle Scholar
  36. 36.
    Schluns KS, Nowak EC, Cabrera-Hernandez A, Puddington L, Lefrancois L, Aguila HL (2004) Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor alpha expression. Proc Natl Acad Sci USA 101:5616–5621PubMedGoogle Scholar
  37. 37.
    Giuliani M, Giron-Michel J, Negrini S, Vacca P, Durali D, Caignard A, Le Bousse-Kerdiles C, Chouaib S, Devocelle A, Bahri R et al (2008) Generation of a novel regulatory NK cell subset from peripheral blood CD34+ progenitors promoted by membrane-bound IL-15. PLoS ONE 3:e2241Google Scholar
  38. 38.
    Mrozek E, Anderson P, Caligiuri MA (1996) Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood 87:2632–2640PubMedGoogle Scholar
  39. 39.
    Carson WE, Haldar S, Baiocchi RA, Croce CM, Caligiuri MA (1994) The c-kit ligand suppresses apoptosis of human natural killer cells through the upregulation of bcl-2. Proc Natl Acad Sci USA 91:7553–7557PubMedGoogle Scholar
  40. 40.
    De Smedt M, Hoebeke I, Reynvoet K, Leclercq G, Plum J (2005) Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. Blood 106:3498–3506PubMedGoogle Scholar
  41. 41.
    Le PT, Adams KL, Zaya N, Mathews HL, Storkus WJ, Ellis TM (2001) Human thymic epithelial cells inhibit IL-15- and IL-2-driven differentiation of NK cells from the early human thymic progenitors. J Immunol 166:2194–2201PubMedGoogle Scholar
  42. 42.
    Miller JS, Alley KA, McGlave P (1994) Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitor. Blood 83:2594–2601PubMedGoogle Scholar
  43. 43.
    Galy A, Travis M, Cen D, Chen B (1995) Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 3:459–473PubMedGoogle Scholar
  44. 44.
    Haddad R, Guardiola P, Izac B, Thibault C, Radich J, Delezoide AL, Baillou C, Lemoine FM, Gluckman JC, Pflumio F, Canque B (2004) Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood. Blood 104:3918–3926PubMedGoogle Scholar
  45. 45.
    Ryan DH, Nuccie BL, Ritterman I, Liesveld JL, Abboud CN, Insel RA (1997) Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity. Blood 89:929–940PubMedGoogle Scholar
  46. 46.
    Bennett IM, Zatsepina O, Zamai L, Azzoni L, Mikheeva T, Perussia B (1996) Definition of a natural killer NKR-P1A+/CD56-/CD16- functionally immature human NK cell subset that differentiates in vitro in the presence of interleukin 12. J Exp Med 184:1845–1856PubMedGoogle Scholar
  47. 47.
    Lanier LL, Chang C, Phillips JH (1994) Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J Immunol 153:2417–2428Google Scholar
  48. 48.
    Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, 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 188:2375–2380PubMedGoogle Scholar
  49. 49.
    Loza MJ, Zamai L, Azzoni L, Rosati E, Perussia B (2002) Expression of type 1 (interferon gamma) and type 2 (interleukin-13, interleukin-5) cytokines at distinct stages of natural killer cell differentiation from progenitor cells. Blood 99:1273–1281PubMedGoogle Scholar
  50. 50.
    Borrego F, Masilamani M, Kabat J, Sanni TB, Coligan JE (2005) The cell biology of the human natural killer cell CD94/NKG2A inhibitory receptor. Mol Immunol 42:485–488PubMedGoogle Scholar
  51. 51.
    Parham P (2006) Taking license with natural killer cell maturation and repertoire development. Immunol Rev 214:155–160PubMedGoogle Scholar
  52. 52.
    Yokoyama WM, Kim S (2006) Licensing of natural killer cells by self-major histocompatibility complex class I. Immunol Rev 214:143–154PubMedGoogle Scholar
  53. 53.
    Karre K, Ljunggren HG, Piontek G, Kiessling R (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319:675–678PubMedGoogle Scholar
  54. 54.
    Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH (1986) The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136:4480–4486PubMedGoogle Scholar
  55. 55.
    Carrington M, Martin MP (2006) The impact of variation at the KIR gene cluster on human disease. Curr Top Microbiol Immunol 298:225–257PubMedGoogle Scholar
  56. 56.
    Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100PubMedGoogle Scholar
  57. 57.
    Anderson SK (2006) Transcriptional regulation of NK cell receptors. Curr Top Microbiol Immunol 298:59–75PubMedGoogle Scholar
  58. 58.
    Held W, Clevers H, Grosschedl R (2003) Redundant functions of TCF-1 and LEF-1 during T and NK cell development, but unique role of TCF-1 for Ly49 NK cell receptor acquisition. Eur J Immunol 33:1393–1398PubMedGoogle Scholar
  59. 59.
    Cooley S, Xiao F, Pitt M, Gleason M, McCullar V, Bergemann TL, McQueen KL, Guethlein LA, Parham P, Miller JS (2007) A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature. Blood 110:578–586PubMedGoogle Scholar
  60. 60.
    Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A, Corcuff E, Mortier E, Jacques Y, Spits H, Di Santo JP (2009) IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med 206:25–34PubMedGoogle Scholar
  61. 61.
    Williams NS, Kubota A, Bennett M, Kumar V, Takei F (2000) Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression. Eur J Immunol 30:2074–2082PubMedGoogle Scholar
  62. 62.
    Anfossi N, Andre P, Guia S, Falk CS, Roetynck S, Stewart CA, Breso V, Frassati C, Reviron D, Middleton D et al (2006) Human NK cell education by inhibitory receptors for MHC class I. Immunity 25:331–342PubMedGoogle Scholar
  63. 63.
    Fernandez NC, Treiner E, Vance RE, Jamieson AM, Lemieux S, Raulet DH (2005) A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105:4416–4423PubMedGoogle Scholar
  64. 64.
    Kim S, Poursine-Laurent J, Truscott SM, Lybarger L, Song YJ, Yang L, French AR, Sunwoo JB, Lemieux S, Hansen TH, Yokoyama WM (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436:709–713PubMedGoogle Scholar
  65. 65.
    Furukawa H, Yabe T, Watanabe K, Miyamoto R, Miki A, Akaza T, Tadokoro K, Tohma S, Inoue T, Yamamoto K, Juji T (1999) Tolerance of NK and LAK activity for HLA class I-deficient targets in a TAP1-deficient patient (bare lymphocyte syndrome type I). Hum Immunol 60:32–40PubMedGoogle Scholar
  66. 66.
    Bix M, Liao NS, Zijlstra M, Loring J, Jaenisch R, Raulet D (1991) Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349:329–331PubMedGoogle Scholar
  67. 67.
    Yu J, Heller G, Chewning J, Kim S, Yokoyama WM, Hsu KC (2007) Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands. J Immunol 179:5977–5989PubMedGoogle Scholar
  68. 68.
    Ferlazzo G, Thomas D, Lin SL, Goodman K, Morandi B, Muller WA, Moretta A, Munz C (2004) The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. J Immunol 172:1455–1462PubMedGoogle Scholar
  69. 69.
    Trinchieri G (1989) Biology of natural killer cells. Adv Immunol 47:187–376PubMedGoogle Scholar
  70. 70.
    Whiteside TL, Herberman RB (1994) Role of human natural killer cells in health and disease. Clin Diagn Lab Immunol 1:125–133PubMedGoogle Scholar
  71. 71.
    Lanier LL, Le AM, Phillips JH, Warner NL, Babcock GF (1983) Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol 131:1789–1796PubMedGoogle Scholar
  72. 72.
    Farag SS, Caligiuri MA (2006) Human natural killer cell development and biology. Blood Rev 20:123–137PubMedGoogle Scholar
  73. 73.
    Freud AG, Caligiuri MA (2006) Human natural killer cell development. Immunol Rev 214:56–72PubMedGoogle Scholar
  74. 74.
    Andre P, Spertini O, Guia S, Rihet P, Dignat-George F, Brailly H, Sampol J, Anderson PJ, Vivier E (2000) Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin. Proc Natl Acad Sci USA 97:3400–3405PubMedGoogle Scholar
  75. 75.
    Caligiuri MA, Zmuidzinas A, Manley TJ, Levine H, Smith KA, Ritz J (1990) Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors. J Exp Med 171: 1509–1526PubMedGoogle Scholar
  76. 76.
    Campbell JJ, Qin S, Unutmaz D, Soler D, Murphy KE, Hodge MR, Wu L, Butcher EC (2001) Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. J Immunol 166:6477–6482PubMedGoogle Scholar
  77. 77.
    Frey M, Packianathan NB, Fehniger TA, Ross ME, Wang WC, Stewart CC, Caligiuri MA, Evans SS (1998) Differential expression and function of L-selectin on CD56bright and CD56dim natural killer cell subsets. J Immunol 161:400–408PubMedGoogle Scholar
  78. 78.
    Jacobs R, Hintzen G, Kemper A, Beul K, Kempf S, Behrens G, Sykora KW, Schmidt RE (2001) CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells. Eur J Immunol 31:3121–3127PubMedGoogle Scholar
  79. 79.
    Matos ME, Schnier GS, Beecher MS, Ashman LK, William DE, Caligiuri MA (1993) Expression of a functional c-kit receptor on a subset of natural killer cells. J Exp Med 178:1079–1084PubMedGoogle Scholar
  80. 80.
    Nagler A, Lanier LL, Phillips JH (1990) Constitutive expression of high affinity interleukin 2 receptors on human CD16-natural killer cells in vivo. J Exp Med 171:1527–1533PubMedGoogle Scholar
  81. 81.
    Voss SD, Daley J, Ritz J, Robertson MJ (1998) Participation of the CD94 receptor complex in costimulation of human natural killer cells. J Immunol 160:1618–1626PubMedGoogle Scholar
  82. 82.
    Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, Carson WE, Caligiuri MA (2001) Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood 97:3146–3151PubMedGoogle Scholar
  83. 83.
    Nagler A, Lanier LL, Cwirla S, Phillips JH (1989) Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol 143:3183–3191PubMedGoogle Scholar
  84. 84.
    Chklovskaia E, Nowbakht P, Nissen C, Gratwohl A, Bargetzi M, Wodnar-Filipowicz A (2004) Reconstitution of dendritic and natural killer-cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand. Blood 103:3860–3868PubMedGoogle Scholar
  85. 85.
    Gottschalk LR, Bray RA, Kaizer H, Gebel HM (1990) Two populations of CD56 (Leu-19)+/CD16+ cells in bone marrow transplant recipients. Bone Marrow Transplant 5: 259–264PubMedGoogle Scholar
  86. 86.
    Jacobs R, Stoll M, Stratmann G, Leo R, Link H, Schmidt RE (1992) CD16- CD56+ natural killer cells after bone marrow transplantation. Blood 79:3239–3244PubMedGoogle Scholar
  87. 87.
    Romagnani C, Juelke K, Falco M, Morandi B, D'Agostino A, Costa R, Ratto G, Forte G, Carrega P, Lui G et al (2007) CD56brightCD16- killer Ig-like receptor- NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation. J Immunol 178:4947–4955PubMedGoogle Scholar
  88. 88.
    Chan A, Hong DL, Atzberger A, Kollnberger S, Filer AD, Buckley CD, McMichael A, Enver T, Bowness P (2007) CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts. J Immunol 179:89–94PubMedGoogle Scholar
  89. 89.
    Di Santo JP (2008) Natural killer cells: diversity in search of a niche. Nat Immunol 9: 473–475PubMedGoogle Scholar
  90. 90.
    Freud AG, Becknell B, Roychowdhury S, Mao HC, Ferketich AK, Nuovo GJ, Hughes TL, Marburger TB, Sung J, Baiocchi RA et al (2005) A human CD34(+) subset resides in lymph nodes and differentiates into CD56bright natural killer cells. Immunity 22:295–304PubMedGoogle Scholar
  91. 91.
    Freud AG, Yokohama A, Becknell B, Lee MT, Mao HC, Ferketich AK, Caligiuri MA (2006) Evidence for discrete stages of human natural killer cell differentiation in vivo. J Exp Med 203:1033–1043PubMedGoogle Scholar
  92. 92.
    Grzywacz B, Kataria N, Sikora M, Oostendorp RA, Dzierzak EA, Blazar BR, Miller JS, Verneris MR (2006) Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells. Blood 108:3824–3833PubMedGoogle Scholar
  93. 93.
    Veinotte LL, Halim TY, Takei F (2008) Unique subset of natural killer cells develops from progenitors in lymph node. Blood 111:4201–4208PubMedGoogle Scholar
  94. 94.
    Mebius RE, Rennert P, Weissman IL (1997) Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity 7:493–504PubMedGoogle Scholar
  95. 95.
    Eberl G, Littman DR (2003) The role of the nuclear hormone receptor RORgammat in the development of lymph nodes and Peyer's patches. Immunol Rev 195:81–90PubMedGoogle Scholar
  96. 96.
    Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, Fibbe WE, Cornelissen JJ, Spits H (2009) Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 10:66–74PubMedGoogle Scholar
  97. 97.
    Fehniger TA, Cooper MA, Nuovo GJ, Cella M, Facchetti F, Colonna M, Caligiuri MA (2003) CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood 101:3052–3057PubMedGoogle Scholar
  98. 98.
    Gallatin WM, Weissman IL, Butcher EC (1983) A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature 304:30–34PubMedGoogle Scholar
  99. 99.
    Kim CH, Pelus LM, Appelbaum E, Johanson K, Anzai N, Broxmeyer HE (1999) CCR7 ligands, SLC/6Ckine/Exodus2/TCA4 and CKbeta-11/MIP-3beta/ELC, are chemoattractants for CD56(+)CD16(-) NK cells and late stage lymphoid progenitors. Cell Immunol 193:226–235PubMedGoogle Scholar
  100. 100.
    Martin-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, Sallusto F (2004) Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol 5:1260–1265PubMedGoogle Scholar
  101. 101.
    Mailliard RB, Alber SM, Shen H, Watkins SC, Kirkwood JM, Herberman RB, Kalinski P (2005) IL-18-induced CD83+CCR7+ NK helper cells. J Exp Med 202:941–953PubMedGoogle Scholar
  102. 102.
    Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640PubMedGoogle Scholar
  103. 103.
    Morandi B, Bougras G, Muller WA, Ferlazzo G, Munz C (2006) NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN-gamma secretion. Eur J Immunol 36:2394–2400PubMedGoogle Scholar
  104. 104.
    Garni-Wagner BA, Witte PL, Tutt MM, Kuziel WA, Tucker PW, Bennett M, Kumar V (1990) Natural killer cells in the thymus. Studies in mice with severe combined immune deficiency. J Immunol 144:796–803Google Scholar
  105. 105.
    Michon JM, Caligiuri MA, Hazanow SM, Levine H, Schlossman SF, Ritz J (1988) Induction of natural killer effectors from human thymus with recombinant IL-2. J Immunol 140: 3660–3667PubMedGoogle Scholar
  106. 106.
    Mingari MC, Poggi A, Bellomo R, Pella N, Moretta L (1991) Thymic origin of some natural killer cells: clonal proliferation of human CD3–16+ cells from CD3–4-8- thymocyte precursors requires the presence of H9 leukemic cells. Int J Clin Lab Res 21:176–178PubMedGoogle Scholar
  107. 107.
    Sanchez MJ, Spits H, Lanier LL, Phillips JH (1993) Human natural killer cell committed thymocytes and their relation to the T cell lineage. J Exp Med 178:1857–1866PubMedGoogle Scholar
  108. 108.
    Barcena A, Muench MO, Galy AH, Cupp J, Roncarolo MG, Phillips JH, Spits H (1993) Phenotypic and functional analysis of T-cell precursors in the human fetal liver and thymus: CD7 expression in the early stages of T- and myeloid-cell development. Blood 82:3401–3414PubMedGoogle Scholar
  109. 109.
    Carlyle JR, Michie AM, Furlonger C, Nakano T, Lenardo MJ, Paige CJ, Zuniga-Pflucker JC (1997) Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes. J Exp Med 186:173–182PubMedGoogle Scholar
  110. 110.
    Michie AM, Carlyle JR, Schmitt TM, Ljutic B, Cho SK, Fong Q, Zuniga-Pflucker JC (2000) Clonal characterization of a bipotent T cell and NK cell progenitor in the mouse fetal thymus. J Immunol 164:1730–1733PubMedGoogle Scholar
  111. 111.
    Vosshenrich CA, Garcia-Ojeda ME, Samson-Villeger SI, Pasqualetto V, Enault L, Richard-Le Goff O, Corcuff E, Guy-Grand D, Rocha B, Cumano A et al (2006) A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol 7:1217–1224PubMedGoogle Scholar
  112. 112.
    De Smedt M, Taghon T, Van de Walle I, De Smet G, Leclercq G, Plum J (2007) Notch signaling induces cytoplasmic CD3 epsilon expression in human differentiating NK cells. Blood 110:2696–2703PubMedGoogle Scholar
  113. 113.
    Hanna J, Bechtel P, Zhai Y, Youssef F, McLachlan K, Mandelboim O (2004) Novel insights on human NK cells' immunological modalities revealed by gene expression profiling. J Immunol 173:6547–6563PubMedGoogle Scholar
  114. 114.
    Di Santo JP, Vosshenrich CA (2006) Bone marrow versus thymic pathways of natural killer cell development. Immunol Rev 214:35–46PubMedGoogle Scholar
  115. 115.
    Carotta S, Brady J, Wu L, Nutt SL (2006) Transient Notch signaling induces NK cell potential in Pax5-deficient pro-B cells. Eur J Immunol 36:3294–3304PubMedGoogle Scholar
  116. 116.
    Huang J, Garrett KP, Pelayo R, Zuniga-Pflucker JC, Petrie HT, Kincade PW (2005) Propensity of adult lymphoid progenitors to progress to DN2/3 stage thymocytes with Notch receptor ligation. J Immunol 175:4858–4865PubMedGoogle Scholar
  117. 117.
    Rolink AG, Balciunaite G, Demoliere C, Ceredig R (2006) The potential involvement of Notch signaling in NK cell development. Immunol Lett 107:50–57PubMedGoogle Scholar
  118. 118.
    Radtke F, Wilson A, Ernst B, MacDonald HR (2002) The role of Notch signaling during hematopoietic lineage commitment. Immunol Rev 187:65–74PubMedGoogle Scholar
  119. 119.
    Poggi A, Biassoni R, Pella N, Paolieri F, Bellomo R, Bertolini A, Moretta L, Mingari MC (1990) In vitro expansion of CD3/TCR- human thymocyte populations that selectively lack CD3 delta gene expression: a phenotypic and functional analysis. J Exp Med 172:1409–1418PubMedGoogle Scholar
  120. 120.
    Leon F, Roldan E, Sanchez L, Camarero C, Bootello A, Roy G (2003) Human small-intestinal epithelium contains functional natural killer lymphocytes. Gastroenterology 125:345–356PubMedGoogle Scholar
  121. 121.
    Lundqvist C, Baranov V, Hammarstrom S, Athlin L, Hammarstrom ML (1995) Intra-epithelial lymphocytes: evidence for regional specialization and extrathymic T cell maturation in the human gut epithelium. Int Immunol 7:1473–1487PubMedGoogle Scholar
  122. 122.
    Tagliabue A, Befus AD, Clark DA, Bienenstock J (1982) Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria. J Exp Med 155:1785–1796PubMedGoogle Scholar
  123. 123.
    Chinen H, Matsuoka K, Sato T, Kamada N, Okamoto S, Hisamatsu T, Kobayashi T, Hasegawa H, Sugita A, Kinjo F et al (2007) Lamina propria c-kit+ immune precursors reside in human adult intestine and differentiate into natural killer cells. Gastroenterology 133:559–573PubMedGoogle Scholar
  124. 124.
    Luci C, Reynders A, Ivanov II, Cognet C, Chiche L, Chasson L, Hardwigsen J, Anguiano E, Banchereau J, Chaussabel D et al (2009) Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol 10:75–82PubMedGoogle Scholar
  125. 125.
    Sanos SL, Bui VL, Mortha A, Oberle K, Heners C, Johner C, Diefenbach A (2009) RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 10:83–91PubMedGoogle Scholar
  126. 126.
    Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, Mention JJ, Thiam K, Cerf-Bensussan N, Mandelboim O et al (2008) Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958–970PubMedGoogle Scholar
  127. 127.
    Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457:722–725PubMedGoogle Scholar
  128. 128.
    Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29:947–957PubMedGoogle Scholar
  129. 129.
    Murray AM, Simm B, Beagley KW (1998) Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development. Cytokine 10:337–345PubMedGoogle Scholar
  130. 130.
    Sander GR, Powell BC (2004) Expression of notch receptors and ligands in the adult gut. J Histochem Cytochem 52:509–516PubMedGoogle Scholar
  131. 131.
    Schroder N, Gossler A (2002) Expression of Notch pathway components in fetal and adult mouse small intestine. Gene Expr Patterns 2:247–250PubMedGoogle Scholar
  132. 132.
    Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A, Manz MG (2004) Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304:104–107PubMedGoogle Scholar
  133. 133.
    Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, Spits H (2006) Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in "human immune system" Rag2(-/-)gammac(-/-) mice. Blood 108:238–245PubMedGoogle Scholar
  134. 134.
    Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130PubMedGoogle Scholar
  135. 135.
    Melkus MW, Estes JD, Padgett-Thomas A, Gatlin J, Denton PW, Othieno FA, Wege AK, Haase AT, Garcia JV (2006) Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med 12:1316–1322PubMedGoogle Scholar
  136. 136.
    Kalberer CP, Siegler U, Wodnar-Filipowicz A (2003) Human NK cell development in NOD/SCID mice receiving grafts of cord blood CD34+ cells. Blood 102:127–135PubMedGoogle Scholar
  137. 137.
    Carson WE, Giri JG, Lindemann MJ, Linett ML, Ahdieh M, Paxton R, Anderson D, Eisenmann J, Grabstein K, Caligiuri MA (1994) Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med 180:1395–1403PubMedGoogle Scholar
  138. 138.
    Miller JS, McCullar V (2001) Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2. Blood 98:705–713PubMedGoogle Scholar
  139. 139.
    Cooley S, McCullar V, Wangen R, Bergemann TL, Spellman S, Weisdorf DJ, Miller JS (2005) KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation. Blood 106:4370–4376PubMedGoogle Scholar
  140. 140.
    Shilling HG, McQueen KL, Cheng NW, Shizuru JA, Negrin RS, Parham P (2003) Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation. Blood 101:3730–3740PubMedGoogle Scholar
  141. 141.
    Zimmer J, Bausinger H, Andres E, Donato L, Hanau D, Hentges F, Moretta A, de la Salle H (2007) Phenotypic studies of natural killer cell subsets in human transporter associated with antigen processing deficiency. PLoS ONE 2:e1033Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Nicholas D. Huntington
    • 1
    • 2
  • Jean-Jacques Mention
    • 1
    • 2
  • Christian Vosshenrich
    • 1
    • 2
  • Naoko Satoh-Takayama
    • 1
    • 2
  • James P. Di Santo
    • 1
    • 2
    Email author
  1. 1.Cytokines and Lymphoid Development Unit Institut PasteurParisFrance
  2. 2.Inserm U668ParisFrance

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