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Bridging Innate NK Cell Functions with Adaptive Immunity

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Crossroads between Innate and Adaptive Immunity III

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 780))

Abstract

Killer Ig-like receptors (KIRs) are major human NK receptors displaying either inhibitory or activating functions which recognize allotypic determinants of HLA-class I molecules. Surprisingly, NK cell treatment with CpG-ODN (TLR9 ligands) results in selective down-modulation of KIR3DL2, its co-internalization with CpG-ODN and its translocation to TLR9-rich early endosomes. This novel KIR-associated function may offer clues to better understand the possible role of certain KIRs and also emphasizes the involvement of NK cells in the course of microbial infections. NK cells are involved not only in innate immune responses against viruses and tumors but also participate in the complex network of cell-to cell interaction that leads to the development of adaptive immune responses. In this context the interaction of NK cells with DC appears to play a crucial role in the acquisition of CCR7, a chemokine receptor that enables NK cells to migrate towards lymph nodes in response to CCL19 and/or CCL21. Analysis of NK cell clones revealed that KIR-mismatched but not KIR-matched NK cells acquire CCR7. These data have important implications in haploidentical haematopoietic stem cell transplantation (HSCT), in which KIR-mismatched NK cells may acquire the ability to migrate to secondary lymphoid compartments (SLCs), where they can kill recipient’s antigen presenting cells (APCs) and T cells thus preventing graft versus host (and host vs. graft) reactions.

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References

  1. Moretta A, Bottino C, Vitale M et al (1996) Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol 14:619–648

    Article  PubMed  CAS  Google Scholar 

  2. Braud VM, Allan DS, O’Callaghan CA et al (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391:795–799

    Article  PubMed  CAS  Google Scholar 

  3. Moretta A, Bottino C, Vitale M et al (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  PubMed  CAS  Google Scholar 

  4. Moretta L, Biassoni R, Bottino C et al (2000) Human NK-cell receptors. Immunol Today 21:420–422

    Article  PubMed  CAS  Google Scholar 

  5. Bottino C, Falco M, Parolini S et al (2001) NTB-A, a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked lymphoproliferative disease. J Exp Med 194:235–246

    Article  PubMed  CAS  Google Scholar 

  6. Bottino C, Castriconi R, Moretta L et al (2005) Cellular ligands of activating NK receptors. Trends Immunol 26:221–226

    Article  PubMed  CAS  Google Scholar 

  7. Raulet DH (2003) Roles of the NKG2D immuno-receptor and its ligands. Nat Rev Immunol 3:781–790

    Article  PubMed  CAS  Google Scholar 

  8. Agaugue S, Marcenaro E, Ferranti B et al (2008) Human natural killer cells exposed to IL-2, IL-12, IL-18, or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells. Blood 112:1776–1783

    Article  PubMed  CAS  Google Scholar 

  9. Marcenaro E, Della Chiesa M, Bellora F et al (2005) IL-12 or IL-4 prime human NK cells to mediate functionally divergent interactions with dendritic cells or tumors. J Immunol 174:3992–3998

    PubMed  CAS  Google Scholar 

  10. Marcenaro E, Ferranti B, Falco M et al (2008) Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC. Int Immunol 20:1155–1167

    Article  PubMed  CAS  Google Scholar 

  11. Sivori S, Falco M, Della Chiesa M et al (2004) CpG and double-stranded RNA trigger human NK cells by toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells. Proc Natl Acad Sci USA 101:10116–10121

    Article  PubMed  CAS  Google Scholar 

  12. Colonna M, Samaridis J (1995) Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science 268:405–408

    Article  PubMed  CAS  Google Scholar 

  13. Lanier LL (1998) NK cell receptors. Annu Rev Immunol 16:359–393

    Article  PubMed  CAS  Google Scholar 

  14. Moretta A, Vitale M, Bottino C et al (1993) P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J Exp Med 178:597–604

    Article  PubMed  CAS  Google Scholar 

  15. Moretta L, Moretta A (2004) Killer immunoglobulin-like receptors. Curr Opin Immunol 16:626–633

    Article  PubMed  CAS  Google Scholar 

  16. Wagtmann N, Biassoni R, Cantoni C et al (1995) Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity 2:439–449

    Article  PubMed  CAS  Google Scholar 

  17. Biassoni R, Cantoni C, Falco M et al (1996) The human leukocyte antigen (HLA)-C-specific “activatory” or “inhibitory” natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions. J Exp Med 183:645–650

    Article  PubMed  CAS  Google Scholar 

  18. Moretta A, Sivori S, Vitale M et al (1995) Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells. J Exp Med 182:875–884

    Article  PubMed  CAS  Google Scholar 

  19. Chewning JH, Gudme CN, Hsu KC et al (2007) KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol 179:854–868

    PubMed  CAS  Google Scholar 

  20. Stewart CA, Laugier-Anfossi F, Vély F et al (2005) Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA 102:13224–13229

    Article  PubMed  CAS  Google Scholar 

  21. Vilches C, Parham P (2002) KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 20:217–251

    Article  PubMed  CAS  Google Scholar 

  22. Bottino C, Sivori S, Vitale M et al (1996) A novel surface molecule homologous to the p58/p50 family of receptors is selectively expressed on a subset of human natural killer cells and induces both triggering of cell functions and proliferation. Eur J Immunol 26:1816–1824

    Article  PubMed  CAS  Google Scholar 

  23. Della Chiesa M, Romeo E, Falco M et al (2008) Evidence that the KIR2DS5 gene codes for a surface receptor triggering natural killer cell function. Eur J Immunol 38:2284–2289

    Article  PubMed  CAS  Google Scholar 

  24. Estefania E, Flores R, Gomez-Lozano N et al (2007) Human KIR2DL5 is an inhibitory receptor expressed on the surface of NK and T lymphocyte subsets. J Immunol 178:4402–4410

    PubMed  CAS  Google Scholar 

  25. Kikuchi-Maki A, Yusa S, Catina TL et al (2003) KIR2DL4 is an IL-2-regulated NK cell receptor that exhibits limited expression in humans but triggers strong IFN-gamma production. J Immunol 171:3415–3425

    PubMed  CAS  Google Scholar 

  26. Thananchai H, Gillespie G, Martin MP et al (2007) Cutting edge: allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol 178:33–37

    PubMed  CAS  Google Scholar 

  27. Dohring C, Scheidegger D, Samaridis J et al (1996) A human killer inhibitory receptor specific for HLA-A1,2. J Immunol 156:3098–3101

    PubMed  CAS  Google Scholar 

  28. Pende D, Biassoni R, Cantoni C et al (1996) The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer. J Exp Med 184:505–518

    Article  PubMed  CAS  Google Scholar 

  29. Litwin V, Gumperz J, Parham P et al (1994) NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules. J Exp Med 180:537–543

    Article  PubMed  CAS  Google Scholar 

  30. Rajagopalan S, Bryceson YT, Kuppusamy SP et al (2006) Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol 4:e9

    Article  PubMed  Google Scholar 

  31. Ljunggren HG, Kärre K (1990) In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today 11:237–244

    Article  PubMed  CAS  Google Scholar 

  32. Anfossi N, Andre P, Guia S et al (2006) Human NK cell education by inhibitory receptors for MHC class I. Immunity 25:331–342

    Article  PubMed  CAS  Google Scholar 

  33. Latz E, Schoenemeyer A, Visintin A et al (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5:190–198

    Article  PubMed  CAS  Google Scholar 

  34. Leifer CA, Kennedy MN, Mazzoni A et al (2004) TLR9 is localized in the endoplasmic reticulum prior to stimulation. J Immunol 173:1179–1183

    PubMed  CAS  Google Scholar 

  35. Krieg AM (2002) CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20:709–760

    Article  PubMed  CAS  Google Scholar 

  36. Sanjuan MA, Rao N, Lai KT et al (2006) CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion. J Cell Biol 172:1057–1068

    Article  PubMed  CAS  Google Scholar 

  37. Sivori S, Falco M, Carlomagno S et al. (2010) A novel KIR-associated function: evidence that CpG DNA uptake and shuttling to early endosomes is mediated by KIR3DL2. Blood 116:1637–1647

    Google Scholar 

  38. Khakoo SI, Geller R, Shin S et al (2002) The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer. J Exp Med 196:911–921

    Article  PubMed  CAS  Google Scholar 

  39. Wilson MJ, Torkar M, Haude A et al (2000) Plasticity in the organization and sequences of human KIR/ILT gene families. Proc Natl Acad Sci USA 97:4778–4783

    Article  PubMed  CAS  Google Scholar 

  40. Fehniger TA, Cooper MA, Nuovo GJ et al (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

    Article  PubMed  CAS  Google Scholar 

  41. Ferlazzo G, Thomas D, Lin SL et al (2004) The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. J Immunol 172:1455–1462

    PubMed  CAS  Google Scholar 

  42. Moser B, Loetscher P (2001) Lymphocyte traffic control by chemokines. Nat Immunol 2:123–128

    Article  PubMed  CAS  Google Scholar 

  43. Della Chiesa M, Vitale M, Carlomagno S et al (2003) The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors. Eur J Immunol 33:1657–1666

    Article  PubMed  CAS  Google Scholar 

  44. Della Chiesa M, Sivori S, Castriconi R et al (2005) Pathogen-induced private conversations between natural killer and dendritic cells. Trends Microbiol 13:128–136

    Article  PubMed  CAS  Google Scholar 

  45. Moretta A (2002) Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol 2:957–964

    Article  PubMed  CAS  Google Scholar 

  46. Moretta A, Marcenaro E, Parolini S et al (2008) NK cells at the interface between innate and adaptive immunity. Cell Death Differ 15:226–233

    Article  PubMed  CAS  Google Scholar 

  47. Marcenaro E, Della Chiesa M, Pesce S et al (2009) The NK/DC complot. Adv Exp Med Biol 633:7–16

    Article  PubMed  CAS  Google Scholar 

  48. Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640

    Article  PubMed  CAS  Google Scholar 

  49. Parolini S, Santoro A, Marcenaro E et al (2007) The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues. Blood 109:3625–3632

    Article  PubMed  CAS  Google Scholar 

  50. Robertson MJ (2002) Role of chemokines in the biology of natural killer cells. J Leukoc Biol 71:173–183

    PubMed  CAS  Google Scholar 

  51. Vitale M, Della Chiesa M, Carlomagno S et al (2004) The small subset of CD56brightCD16- natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells. Eur J Immunol 34:1715–1722

    Article  PubMed  CAS  Google Scholar 

  52. Sallusto F, Mackay CR, Lanzavecchia A (2000) The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 18:593–620

    Article  PubMed  CAS  Google Scholar 

  53. Mailliard RB, Alber SM, Shen H et al (2005) IL-18-induced CD83+CCR7+ NK helper cells. J Exp Med 202:941–953

    Article  PubMed  CAS  Google Scholar 

  54. Ferlazzo G, Munz C (2004) NK cell compartments and their activation by dendritic cells. J Immunol 172:1333–1339

    PubMed  CAS  Google Scholar 

  55. Ferlazzo G, Tsang ML, Moretta L et al (2002) Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 195:343–351

    Article  PubMed  CAS  Google Scholar 

  56. Gerosa F, Baldani-Guerra B, Nisii C et al (2002) Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med 195:327–333

    Article  PubMed  CAS  Google Scholar 

  57. Piccioli D, Sbrana S, Melandri E et al (2002) Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med 195:335–341

    Article  PubMed  CAS  Google Scholar 

  58. Bajenoff M, Glaichenhaus N, Germain RN (2008) Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone. J Immunol 181:3947–3954

    PubMed  CAS  Google Scholar 

  59. Marcenaro E, Cantoni C, Pesce S et al (2009) Uptake of CCR7 and acquisition of migratory properties by human KIR+NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction. Blood 114:4108–4116

    Article  PubMed  CAS  Google Scholar 

  60. Davis DM (2007) Intercellular transfer of cell-surface proteins is common and can affect many stages of an immune response. Nat Rev Immunol 7:238–243

    Article  PubMed  CAS  Google Scholar 

  61. Hudrisier D, Riond J, Mazarguil H et al (2001) Cutting edge: CTLs rapidly capture membrane fragments from target cells in a TCR signaling-dependent manner. J Immunol 166:3645–3649

    PubMed  CAS  Google Scholar 

  62. Joly E, Hudrisier D (2003) What is trogocytosis and what is its purpose? Nat Immunol 4:815

    Article  PubMed  CAS  Google Scholar 

  63. Mack M, Kleinschmidt A, Bruhl H et al (2000) Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immuno-deficiency virus 1 infection. Nat Med 6:769–775

    Article  PubMed  CAS  Google Scholar 

  64. Tabiasco J, Espinosa E, Hudrisier D et al (2002) Active trans-synaptic capture of membrane fragments by natural killer cells. Eur J Immunol 32:1502–1508

    Article  PubMed  CAS  Google Scholar 

  65. Moretta A, Bottino C, Pende D et al (1990) Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules: correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition. J Exp Med 172:1589–1598

    Article  PubMed  CAS  Google Scholar 

  66. Moretta A, Locatelli F, Moretta L (2008) Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias. Immunol Rev 224:58–69

    Article  PubMed  CAS  Google Scholar 

  67. Pende D, Marcenaro S, Falco M et al (2009) Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haplo-identical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood 113:3119–3129

    Article  PubMed  CAS  Google Scholar 

  68. Ruggeri L, Mancusi A, Capanni M et al (2007) Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood 110:433–440

    Article  PubMed  CAS  Google Scholar 

  69. Velardi A, Ruggeri L, Moretta A et al (2002) NK cells: a lesson from mismatched hematopoietic transplantation. Trends Immunol 23:438–444

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.): MFAG project n. 6383 (S.S.) and IG project n. 10643 (A.M.); Istituto Superiore di Sanità (I.S.S.), agreement n. 40G.41; Ministero della Sanità, Ministero dell’Istruzione, dell’Università e della Ricerca Scientifica e Tecnologica (MIUR-PRIN 2006/project 2006061378_003; MIUR-FIRB 2003 project RBLA039LSF_001) and Progetto di Ricerca di Ateneo 2008 dell’Università di Genova, project E.M.

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Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale-sezione Istologia, Università degli Studi di Genova, Via G.B. Marsano 10, 16132, Genova, Italy

    Alessandro Moretta

  2. Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, V.le Benedetto XV, 16132, Genova, Italy

    Alessandro Moretta

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  1. Emanuela Marcenaro
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  2. Simona Carlomagno
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  3. Silvia Pesce
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  4. Alessandro Moretta
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  5. Simona Sivori
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Correspondence to Alessandro Moretta .

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Editors and Affiliations

  1. Emory Vaccine Center &, Yerkes National Primate Research Center, Emory University, Gatewood Rd. 954, Atlanta, 30329, Georgia, USA

    Bali Pulendran

  2. College of Medicine, Department Microbiology & Immunology, Drexel University, Queen Lane 2900, Philadelphia, 19129, Pennsylvania, USA

    Peter D. Katsikis

  3. , Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immun, Athena Circle 9420, La Jolla, 92037, USA

    Stephen P. Schoenberger

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Marcenaro, E., Carlomagno, S., Pesce, S., Moretta, A., Sivori, S. (2011). Bridging Innate NK Cell Functions with Adaptive Immunity. In: Pulendran, B., Katsikis, P., Schoenberger, S. (eds) Crossroads between Innate and Adaptive Immunity III. Advances in Experimental Medicine and Biology, vol 780. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5632-3_5

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