Conclusions
NK cells were initially thought to be endowed with a particular migratory pattern and to mainly circulate in the blood. The recent findings reviewed here highlight that NK cells can exhibit different predilictions for tissue compartments, i.e., lymph nodes, inflamed tissues, etc., where they can play an important role as active participants in directing DC maturation and T cell response polarization and/or as cytotoxic effector cells.
The mechanisms regulating tissue-selective NK cell homing and functional specialization are just starting to be unraveled, but the importance of tissue microenvironment is becoming increasingly clear. An example is given by decidual NK cells whose differentiation, accumulation and functional program are under hormonal influence.
Chapter PDF
Keywords
- Natural Killer Cell
- Focal Adhesion Kinase
- Chemokine Receptor
- Human Natural Killer Cell
- Natural Killer Cell Subset
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.
References
Trinchieri G (1989) Biology of natural killer cells. Adv Immunol 47: 187–376
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: 295–304
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: 3052–3057
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: 1260–1265
Biron CA (1997) Activation and function of natural killer cell responses during viral infection. Curr Opin Immunol 9: 24–34
Fogler WE, Volker K, McCormick KL, Watanabe M, Ortaldo JR, Wiltrout RH(1996) NK cell infiltration into lung, liver, and subcutaneous B16 melanoma is mediated by VCAM-1/VLA-4 interaction. J Immunol 156:4707–4714
Raulet DH, Vance RE, McMahon CW (2001) Regulation of the natural killer cell receptor repertoire. Annu Rev Immunol 19: 291–330
Lanier LL (2005) NK Cell Recognition. Annu Rev Immunol 23: 225–274
Raulet DH (2003) Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol 3: 781–790
Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436: 1186–1190
Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19: 197–223
Shibuya K, Lanier LL, Phillips JH, Ochs HD, Shimizu K, Nakayama E, Nakauchi H, Shibuya A (1999) Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity 11: 615–623
Bottino C, Castriconi R, Pende D, Rivera P, Nanni M, Carnemolla B, Cantoni C, Grassi J, Marcenaro S, Reymond N et al (2003) Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med 198: 557–567
McQueen KL, Parham P (2002) Variable receptors controlling activation and inhibition of NK cells. Curr Opin Immunol 14: 615–621
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: 3146–3151
Loza MJ, Perussia B (2004) The IL-12 signature: NK cell terminal CD56+ high stage and effector functions. J Immunol 172: 88–96
Kunkel EJ, Butcher EC (2002) Chemokines and the tissue-specific migration of lymphocytes. Immunity 16: 1–4
Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76: 301–314
Baggiolini M, Dewald B, Moser B (1997) Human chemokines: an update. Annu Rev Immunol 15: 675–705
Mantovani A (1999) The chemokine system: redundancy for robust outputs. Immunol Today 20: 254–257
Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18: 217–242
Clark EA, Brugge JS (1995) Integrins and signal transduction pathways: the road taken. Science 268: 233–239
De Filippi P, Gismondi A, Santoni A, Tarone G (1997) Signal transduction by integrins. Springer, Austin, TX
Maenpaa A, Jaaskelainen J, Carpen O, Patarroyo M, Timonen T (1993) Expression of integrins and other adhesion molecules on NK cells; impact of IL-2 on short-and longterm cultures. Int J Cancer 53: 850–855
Uksila J, Salmi M, Butcher EC, Tarkkanen J, Jalkanen S (1997) Function of lymphocyte homing-associated adhesion molecules on human natural killer and lymphokine-activated killer cells. J Immunol 158: 1610–1617
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: 400–408
Moore KL, Thompson LF (1992) P-selectin (CD62) binds to subpopulations of human memory T lymphocytes and natural killer cells. Biochem Biophys Res Commun 186: 173–181
Pinola M, Renkonen R, Majuri ML, Tiisala S, Saksela E (1994) Characterization of the E-selectin ligand on NK cells. J Immunol 152: 3586–3594
Snapp KR, Ding H, Atkins K, Warnke R, Luscinskas FW, Kansas GS (1998) A novel Pselectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P-and Lselectin. Blood 91: 154–164
Yago T, Tsukuda M, Fukushima H, Yamaoka H, Kurata-Miura K, Nishi T, Minami M (1998) IL-12 promotes the adhesion of NK cells to endothelial selectins under flow conditions. J Immunol 161: 1140–1145
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: 3400–3405
Gismondi A, Morrone S, Humphries MJ, Piccoli M, Frati L, Santoni A (1991) Human natural killer cells express VLA-4 and VLA-5, which mediate their adhesion to fibronectin. J Immunol 146: 384–392
Mainiero F, Gismondi A, Milella M, Morrone S, Palmieri G, Piccoli M, Frati L, Santoni A (1994) Long term activation of natural killer cells results in modulation of beta1-integrin expression and function. J Immunol 152: 446–454
Gismondi A, Mainiero F, Morrone S, Palmieri G, Piccoli M, Frati L, Santoni A (1992) Triggering through CD16 or phorbol esters enhances adhesion of NK cells to laminin via very late antigen 6. J Exp Med 176: 1251–1257
Perez-Villar JJ, Melero I, Gismondi A, Santoni A, Lopez-Botet M (1996) Functional analysis of alpha1beta1 integrin in human natural killer cells. Eur J Immunol 26: 2023–2029
Allavena P, Paganin C, Martin-Padura I, Peri G, Gaboli M, Dejana E, Marchisio PC, Mantovani A (1991) Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium. J Exp Med 173: 439–448
Schneider MK, Strasser M, Gilli UO, Kocher M, Moser R, Seebach JD (2002) Rolling adhesion of human NK cells to porcine endothelial cells mainly relies on CD49d-CD106 interactions. Transplantation 73: 789–796
Pinola M, Saksela E, Tiisala S, Renkonen R (1994) Human NK cells expressing alpha 4 beta 1/beta 7 adhere to VCAM-1 without preactivation. Scand J Immunol 39: 131–136
Perez-Villar JJ, Zapata JM, Melero I, Postigo A, Sanchez-Madrid E, Lopez-Botet M (1996) Expression and function of alpha 4/beta 7 integrin on human natural killer cells. Immunology 89: 96–104
Rott LS, Briskin MJ, Andrew DP, Berg EL, Butcher EC (1996) A fundamental subdivision of circulating lymphocytes defined by adhesion to mucosal addressin cell adhesion molecule-1. Comparison with vascular cell adhesion molecule-1 and correlation with beta 7 integrins and memory differentiation. J Immunol 156: 3727–3736
Timonen T (1997) Natural killer cells: endothelial interactions, migration and target cell recognition. J Leukoc Biol 62: 693–701
Allavena P, Paganin C, Zhou D, Bianchi G, Sozzani S, Mantovani A (1994) Interleukin-12 is chemotactic for natural killer cells and stimulates their interaction with vascular endothelium. Blood 84: 2261–2268
Morohashi H, Miyawaki T, Nomura H, Kuno K, Murakami S, Matsushima K, Mukaida N (1995) Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells. J Leukoc Biol 57: 180–187
Chuntharapai A, Lee J, Hebert CA, Kim KJ (1994) Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes. J Immunol 153: 5682–5688
Casilli F, Bianchini A, Gloaguen I, Biordi L, Alesse E, Festuccia C, Cavalieri B, Strippoli R, Cervellera MN, Di Bitondo R et al (2005) Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2. Biochem Pharmacol 69: 385–94
Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ et al (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91: 521–530
Yoneda O, Imai T, Goda S, Inoue H, Yamauchi A, Okazaki T, Imai H, Yoshie O, Bloom ET, Domae N, Umehara H (2000) Fractalkine-mediated endothelial cell injury by NK cells. J Immunol 164: 4055–4062
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: 6477–6482
Taub DD, Sayers TJ, Carter CR, Ortaldo JR (1995) Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. J Immunol 155: 3877–3888
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: 226–235
Hodge DL, Schill WB, Wang JM, Blanca I, Reynolds DA, Ortaldo JR, Young HA (2002) IL-2 and IL-12 alter NK cell responsiveness to IFN-gamma-inducible protein 10 by down-regulating CXCR3 expression. J Immunol 168: 6090–6098
Polentarutti N, Allavena P, Bianchi G, Giardina G, Basile A, Sozzani S, Mantovani A, Introna M (1997) IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences. J Immunol 158: 2689–2694
Inngjerdingen M, Damaj B, Maghazachi AA (2001) Expression and regulation of chemokine receptors in human natural killer cells. Blood 97: 367–375
Loetscher P, Seitz M, Clark-Lewis I, Baggiolini M, Moser B (1996) Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release. J Immunol 156: 322–327
Allavena P, Bianchi G, Zhou D, van Damme J, Jilek P, Sozzani S, Mantovani A (1994) Induction of natural killer cell migration by monocyte chemotactic protein-1,-2 and-3. Eur J Immunol 24: 3233–3236
Godiska R, Chantry D, Raport CJ, Sozzani S, Allavena P, Leviten D, Mantovani A, Gray PW (1997) Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells. J Exp Med 185: 1595–1604
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: 941–953
Vicente-Manzanares M, Sanchez-Madrid F (2004) Role of the cytoskeleton during leukocyte responses. Nat Rev Immunol 4: 110–122
Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302: 1704–1709
Perez OD, Mitchell D, Jager GC, Nolan GP (2004) LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells. Blood 104: 1083–1093
Riteau B, Barber DF, Long EO (2003) Vav1 phosphorylation is induced by beta2 integrin engagement on natural killer cells upstream of actin cytoskeleton and lipid raft reorganization. J Exp Med 198: 469–474
Inngjerdingen M, Torgersen KM, Maghazachi AA (2002) Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis. Blood 99: 4318–4325
Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J (1995) Protein tyrosine kinase Pyk-2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions. Nature 376: 737–745
Avraham H, Park S-Y, Schinkmann K, Avraham S (2000) RAFTK/Pyk-2-mediated cellular signalling. Cell Signalling 12: 123–133
Rabinowich H, Manciulea M, Herberman RB, Whiteside TL (1996) Beta1 integrinmediated activation of focal adhesion kinase and its association with Fyn and Zap-70 in human NK cells. J Immunol 157: 3860–3868
Gismondi A, Bisogno L, Mainiero F, Palmieri G, Piccoli M, Frati L, Santoni A (1997) Proline-rich tyrosine kinase-2 activation by beta 1 integrin fibronectin receptor crosslinking and association with paxillin in human natural killer cells. J Immunol 159: 4729–4736
Gismondi A, Jacobelli J, Mainiero F, Paolini R, Piccoli M, Frati L, Santoni A (2000) Cutting edge: functional role for proline-rich tyrosine kinase 2 in NK cell-mediated natural cytotoxicity. J Immunol 164: 2272–2276
Gismondi A, Jacobelli J, Strippoli R, Mainiero F, Soriani A, Cifaldi L, Piccoli M, Frati L, Santoni A (2003) Proline-rich tyrosine kinase 2 and Rac activation by chemokine and integrin receptors controls NK cell transendothelial migration. J Immunol 170: 3065–3073
Sancho D, Nieto M, Llano M, Rodriguez-Fernandez JL, Tejedor R, Avraham S, Cabanas C, Lopez-Botet M, Sanchez-Madrid F (2000) The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK) cell cytotoxic response, and is translocated and activated upon specific target cell recognition and killing. J Cell Biol 149: 1249–1262
al-Aoukaty A, Rolstad B, Maghazachi AA (1999) Recruitment of pleckstrin and phosphoinositide 3-kinase gamma into the cell membranes, and their association with G beta gamma after activation of NK cells with chemokines. J Immunol 162: 3249–3255
Salazar-Mather TP, Orange JS, Biron CA (1998) Early murine cytomegalovirus (MCMV) infection induces liver natural killer (NK) cell inflammation and protection through macrophage inflammatory protein-1α(MIP-1α-dependent pathways. J Exp Med 187: 1–14
Salazar-Mather TP, Hamilton TA, Biron CA (2000) A chemokine-to-cytokine-tochemokine cascade critical in antiviral defense. J Clin Invest 105: 985–993
Zeng X, Moore TA, Newstead MW, Hernandez-Alcoceba R, Tsai WC, Standiford TJ (2003) Intrapulmonary expression of macrophage inflammatory protein 1alpha (CCL3) induces neutrophil and NK cell accumulation and stimulates innate immunity in murine bacterial pneumonia. Infect Immun 71: 1306–1315
Morrison BE, Park SJ, Mooney JM, Mehrad B (2003) Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis. J Clin Invest 112: 1862–1870
Trifilo MJ, Montalto-Morrison C, Stiles LN, Hurst KR, Hardison JL, Manning JE, Masters PS, Lane TE (2004) CXC chemokine ligand 10 controls viral infection in the central nervous system: evidence for a role in innate immune response through recruitment and activation of natural killer cells. J Virol 78: 585–594
Lavergne E, Combadiere B, Bonduelle O, Iga M, Gao JL, Maho M, Boissonnas A, Murphy PM, Debre P, Combadiere C (2003) Fractalkine mediates natural killer-dependent antitumor responses in vivo. Cancer Res 63: 7468–7474
Xin H, Kikuchi T, Andarini S, Ohkouchi S, Suzuki T, Nukiwa T, Huqun, Hagiwara K, Honjo T, Saijo Y (2005) Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells. Eur J Immunol 35: 1371–1380
Robinson LA, Nataraj C, Thomas DW, Cosby JM, Griffiths R, Bautch VL, Patel DD, Coffman TM (2003) The chemokine CX3CL1 regulates NK cell activity in vivo. Cell Immunol 225: 122–130
Jiang D, Liang J, Hodge J, Lu B, Zhu Z, Yu S, Fan J, Gao Y, Yin Z, Homer R et al (2004) Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Invest 114: 291–299
Widney DP, Hu Y, Foreman-Wykert AK, Bui KC, Nguyen TT, Lu B, Gerard C, Miller JF, Smith JB (2005) CXCR3 and its ligands participate in the host response to Bordetella bronchiseptica infection of the mouse respiratory tract but are not required for clearance of bacteria from the lung. Infect Immun 73: 485–493
Shang X, Qiu B, Frait KA, Hu JS, Sonstein J, Curtis JL, Lu B, Gerard C, Chensue SW (2000) Chemokine receptor 1 knockout abrogates natural killer cell recruitment and impairs type-1 cytokines in lymphoid tissue during pulmonary granuloma formation. Am J Pathol 157: 2055–2063
King A, Burrows T, Loke YW (1996–97) Human uterine natural killer cells. Nat Immun 15: 41–52
Whitelaw PF, Croy BA (1996) Granulated lymphocytes of pregnancy. Placenta 17: 533–543
King A (2000) Uterine leukocytes and decidualization. Hum Reprod Update 6: 28–36
Koopman LA, Kopcow HD, Rybalov B, Boyson JE, Orange JS, Schatz F, Masch R, Lockwood CJ, Schachter AD, Park PJ et al (2003) Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J Exp Med 198: 1201–1212
Moffett-King A (2002) Natural killer cells and pregnancy. Nat Rev Immunol 2: 656–663
Hemler ME (2001) Specific tetraspanin functions. J Cell Biol 155: 1103–1107
Hanna J, Wald O, Goldman-Wohl D, Prus D, Markel G, Gazit R, Katz G, Haimov-Kochman R, Fujii N, Yagel S et al (2003) CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells. Blood 102: 1569–1577
Sentman CL, Meadows SK, Wira CR, Eriksson M (2004) Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. J Immunol 173: 6760–6766
Drake PM, Red-Horse K, Fisher SJ (2004) Reciprocal chemokine receptor and ligand expression in the human placenta: implications for cytotrophoblast differentiation. Dev Dyn 229: 877–885
Chantakru S, Kuziel WA, Maeda N, Croy BA (2001) A study on the density and distribution of uterine Natural Killer cells at mid pregnancy in mice genetically-ablated for CCR2, CCR 5 and the CCR5 receptor ligand, MIP-1 alpha. J Reprod Immunol 49: 33–47
Croy BA, Ashkar AA, Foster RA, DiSanto JP, Magram J, Carson D, Gendler SJ, Grusby MJ, Wagner N, Muller W et al (1997) Histological studies of gene-ablated mice support important functional roles for natural killer cells in the uterus during pregnancy. J Reprod Immunol 35: 111–133
Fernekorn U, Butcher EC, Behrends J, Hartz S, Kruse A (2004) Functional involvement of P-selectin and MAdCAM-1 in the recruitment of alpha4beta7-integrin-expressing monocyte-like cells to the pregnant mouse uterus. Eur J Immunol 34: 3423–3433
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Gismondi, A., Santoni, A. (2006). Migration of NK cells. In: Badolato, R., Sozzani, S. (eds) Lymphocyte Trafficking in Health and Disease. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7442-X_6
Download citation
DOI: https://doi.org/10.1007/3-7643-7442-X_6
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-7643-7308-5
Online ISBN: 978-3-7643-7442-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)