Practical NK cell phenotyping and variability in healthy adults

Immunologic Research

Volumn 62, Issue 3, 2015, Pages 341-356

  Angelo, Laura S ^a,b   Banerjee, Pinaki P ^a,b   Monaco Shawver, Linda ^c   Rosen, Joshua B ^d   Makedonas, George ^a,b   Forbes, Lisa R ^a,b   Mace, Emily M ^a,b   Orange, Jordan S ^a,b  

^a TEXAS CHILDREN S HOSPITAL   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^d DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

Flow cytometry; Immunological phenotype; NK cells; Primary immune deficiency

Indexed keywords

ANTIBODY CONJUGATE; CD56 ANTIGEN; CELL MARKER; FLUOROCHROME; IMMUNOGLOBULIN RECEPTOR; KILLER IMMUNOGLOBULIN RECEPTOR; UNCLASSIFIED DRUG; CELL SURFACE RECEPTOR; NCAM1 PROTEIN, HUMAN;

ADULT; ARTICLE; CELL ASSAY; CELL MATURATION; CELL SURFACE; CONTROLLED STUDY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNOPHENOTYPING; LYMPHOCYTE FUNCTION; LYMPHOCYTE SUBPOPULATION; NATURAL KILLER CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; IMMUNOLOGY; METABOLISM; MONONUCLEAR CELL; PROCEDURES;

ADULT; ANTIGENS, CD56; FLOW CYTOMETRY; HUMANS; IMMUNOPHENOTYPING; KILLER CELLS, NATURAL; LEUKOCYTES, MONONUCLEAR; LYMPHOCYTE SUBSETS; RECEPTORS, CELL SURFACE;

EID: 84931576769     PISSN: 0257277X     EISSN: 15590755     Source Type: Journal    
DOI: 10.1007/s12026-015-8664-y     Document Type: Article

References (99)

1. Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, Wara DW, Douglas SD, Luzuriaga K, McFarland EJ, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112:973–80.
2. Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Franco JL, Gaspar HB, Holland SM, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014;5:162.
3. Orange JS. Natural killer cell deficiency. J Allergy Clin Immunol. 2013;132:515–25.
4. Mace EM, Hsu AP, Monaco-Shawver L, Makedonas G, Rosen JB, Dropulic L, Cohen JI, Frenkel EP, Bagwell JC, Sullivan JL, et al. Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56(bright) subset. Blood. 2013;121:2669–77.
5. Freud AG, Caligiuri MA. Human natural killer cell development. Immunol Rev. 2006;214:56–72.
6. Yu J, Freud AG, Caligiuri MA. Location and cellular stages of natural killer cell development. Trends Immunol. 2013;34:573–82.
7. Thielens A, Vivier E, Romagne F. NK cell MHC class I specific receptors (KIR): from biology to clinical intervention. Curr Opin Immunol. 2012;24:239–45.
8. Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008;9:495–502.
9. Marras F, Bozzano F, Ascierto ML, De Maria A. Baseline and dynamic expression of activating NK cell receptors in the control of chronic viral infections: the paradigm of HIV-1 and HCV. Front Immunol. 2014;5:305.
10. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22:633–40.
11. Nagler A, Lanier LL, Cwirla S, Phillips JH. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989;143:3183–91.
12. Morice WG. The immunophenotypic attributes of NK cells and NK-cell lineage lymphoproliferative disorders. Am J Clin Pathol. 2007;127:881–6.
13. Beziat V, Duffy D, Quoc SN, Le Garff-Tavernier M, Decocq J, Combadiere B, Debre P, Vieillard V. CD56bright, CD16+ NK cells: a functional intermediate stage of NK cell differentiation. J Immunol. 2011;186:6753–61.
14. Sabry M, Tsirogianni M, Bakhsh IA, North J, Sivakumaran J, Giannopoulos K, Anderson R, Mackinnon S, Lowdell MW. Leukemic priming of resting NK cells is killer Ig-like receptor independent but requires CD15-mediated CD2 ligation and natural cytotoxicity receptors. J Immunol. 2011;187:6227–34.
15. Nabekura T, Kanaya M, Shibuya A, Fu G, Gascoigne NR, Lanier LL. Costimulatory molecule DNAM-1 is essential for optimal differentiation of memory natural killer cells during mouse cytomegalovirus infection. Immunity. 2014;40:225–34.
16. Yu J, Mao HC, Wei M, Hughes T, Zhang J, Park IK, Liu S, McClory S, Marcucci G, Trotta R, et al. CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets. Blood. 2010;115:274–81.
17. Li Y, Mariuzza RA. Structural basis for recognition of cellular and viral ligands by NK cell receptors. Front Immunol. 2014;5:123.
18. Henney CS, Kuribayashi K, Kern DE, Gillis S. Interleukin-2 augments natural killer cell activity. Nature. 1981;291:335–8.
19. van Montfrans JM, Hoepelman AI, Otto S, van Gijn M, van de Corput L, de Weger RA, Monaco-Shawver L, Banerjee PP, Sanders EA, Jol-van der Zijde CM, et al. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol. 2012;129(787–93):e786.
20. Pradier A, Tabone-Eglinger S, Huber V, Bosshard C, Rigal E, Wehrle-Haller B, Roosnek E. Peripheral blood CD56(bright) NK cells respond to stem cell factor and adhere to its membrane-bound form after upregulation of c-kit. Eur J Immunol. 2014;44:511–20.
21. Lopez-Verges S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, Norris PJ, Nixon DF, Lanier LL. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood. 2010;116:3865–74.
22. Lopez-Verges S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, Houchins JP, Miller S, Kang SM, Norris PJ, et al. Expansion of a unique CD57(+)NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci USA. 2011;108:14725–32.
23. Krzewski K, Coligan JE. Human NK cell lytic granules and regulation of their exocytosis. Front Immunol. 2012;3:335.
24. Millard AL, Valli PV, Stussi G, Mueller NJ, Yung GP, Seebach JD. Brief exercise increases peripheral blood NK Cell counts without immediate functional changes, but impairs their responses to ex vivo stimulation. Front Immunol. 2013;4:125.
25. Gineau L, Cognet C, Kara N, Lach FP, Dunne J, Veturi U, Picard C, Trouillet C, Eidenschenk C, Aoufouchi S, et al. Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. J Clin Investig. 2012;122:821–32.
26. Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N, Dogan OC, Dekker CL, Mackey S, Maecker H, Swan GE, et al. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci Transl Med. 2013;5:208ra145.
27. Shaw RK, Issekutz AC, Fraser R, Schmit P, Morash B, Monaco-Shawver L, Orange JS, Fernandez CV. Bilateral adrenal EBV-associated smooth muscle tumors in a child with a natural killer cell deficiency. Blood. 2012;119:4009–12.
28. Grier JT, Forbes LR, Monaco-Shawver L, Oshinsky J, Atkinson TP, Moody C, Pandey R, Campbell KS, Orange JS. Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J Clin Investig. 2012;122:3769–80.
29. Risma KA, Frayer RW, Filipovich AH, Sumegi J. Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis. J Clin Investig. 2006;116:182–92.
30. Seed B, Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci USA. 1987;84:3365–9.
31. Sewell WA, Brown MH, Dunne J, Owen MJ, Crumpton MJ. Molecular cloning of the human T-lymphocyte surface CD2 (T11) antigen. Proc Natl Acad Sci USA. 1986;83:8718–22.
32. Comerci CJ, Mace EM, Banerjee PP, Orange JS. CD2 promotes human natural killer cell membrane nanotube formation. PLoS One. 2012;7:e47664.
33. Zheng X, Wang Y, Wei H, Sun R, Tian Z. LFA-1 and CD2 synergize for the Erk1/2 activation in the natural killer (NK) cell immunological synapse. J Biol Chem. 2009;284:21280–7.
34. Nakayama K, Kawachi Y, Tokito S, Minami N, Yamamoto R, Imai T, Gachelin G, Nakauchi H. Recent duplication of the two human CD8 beta-chain genes. J Immunol. 1992;148:1919–27.
35. Addison EG, North J, Bakhsh I, Marden C, Haq S, Al-Sarraj S, Malayeri R, Wickremasinghe RG, Davies JK, Lowdell MW. Ligation of CD8alpha on human natural killer cells prevents activation-induced apoptosis and enhances cytolytic activity. Immunology. 2005;116:354–61.
36. Rodriguez AR, Arulanandam BP, Hodara VL, McClure HM, Cobb EK, Salas MT, White R, Murthy KK. Influence of interleukin-15 on CD8+ natural killer cells in human immunodeficiency virus type 1-infected chimpanzees. J Gen Virol. 2007;88(Pt 2):641–51.
37. Corbi AL, Larson RS, Kishimoto TK, Springer TA, Morton CC. Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion. J Exp Med. 1988;167:1597–607.
38. Wang H, Zheng X, Wei H, Tian Z, Sun R. Important role for NKp30 in synapse formation and activation of NK cells. Immunol Invest. 2012;41:367–81.
39. Bryceson YT, March ME, Barber DF, Ljunggren HG, Long EO. Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med. 2005;202:1001–12.
40. Sadhu C, Harris EA, Staunton DE. Enhancement of natural killer cell cytotoxicity by a CD18 integrin-activating antibody. Biochemi Biophys Res Commun. 2007;358:938–41.
41. Corbi AL, Kishimoto TK, Miller LJ, Springer TA. The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B. J Biol Chem. 1988;263:12403–11.
42. Arnaout MA, Remold-O’Donnell E, Pierce MW, Harris P, Tenen DG. Molecular cloning of the alpha subunit of human and guinea pig leukocyte adhesion glycoprotein Mo1: chromosomal localization and homology to the alpha subunits of integrins. Proc Natl Acad Sci USA. 1988;85:2776–80.
43. Orange JS, Chehimi J, Ghavimi D, Campbell D, Sullivan KE. Decreased natural killer (NK) cell function in chronic NK cell lymphocytosis associated with decreased surface expression of CD11b. Clin Immunol. 2001;99:53–64.
44. Arnaout MA, Gupta SK, Pierce MW, Tenen DG. Amino acid sequence of the alpha subunit of human leukocyte adhesion receptor Mo1 (complement receptor type 3). J Cell Biol. 1988;106:2153–8.
45. Ornstein BW, Hill EB, Geurs TL, French AR. Natural killer cell functional defects in pediatric patients with severe and recurrent herpesvirus infections. J Infect Dis. 2013;207:458–68.
46. Ravetch JV, Perussia B. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989;170:481–97.
47. Qiu WQ, de Bruin D, Brownstein BH, Pearse R, Ravetch JV. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science. 1990;248:732–5.
48. Jawahar S, Moody C, Chan M, Finberg R, Geha R, Chatila T. Natural killer (NK) cell deficiency associated with an epitope-deficient Fc receptor type IIIA (CD16-II). Clin Exp Immunol. 1996;103:408–13.
49. Mandelboim O, Malik P, Davis DM, Jo CH, Boyson JE, Strominger JL. Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. Proc Natl Acad Sci USA. 1999;96:5640–4.
50. Axberg I, Ramstedt U, Patarroyo M, Beatty P, Wigzell H. Inhibition of natural killer cell cytotoxicity by a monoclonal antibody directed against adhesion-mediating protein gp 90 (CD18). Scand J Immunol. 1987;26:547–54.
51. Liu JH, Wei S, Blanchard DK, Djeu JY. Restoration of lytic function in a human natural killer cell line by gene transfection. Cell Immunol. 1994;156:24–35.
52. Timonen T, Patarroyo M, Gahmberg CG. CD11a-c/CD18 and GP84 (LB-2) adhesion molecules on human large granular lymphocytes and their participation in natural killing. J Immunol. 1988;141:1041–6.
53. Bigler RD, Bushkin Y, Chiorazzi N. S152 (CD27). A modulating disulfide-linked T cell activation antigen. J Immunol. 1988;141:21–8.
54. Vossen MT, Matmati M, Hertoghs KM, Baars PA, Gent MR, Leclercq G, Hamann J, Kuijpers TW, van Lier RA. CD27 defines phenotypically and functionally different human NK cell subsets. J Immunol. 2008;180:3739–45.
55. Fu B, Tian Z, Wei H. Subsets of human natural killer cells and their regulatory effects. Immunology. 2014;141:483–9.
56. Mitsumoto Y, Oka S, Sakuma H, Inazawa J, Kawasaki T. Cloning and chromosomal mapping of human glucuronyltransferase involved in biosynthesis of the HNK-1 carbohydrate epitope. Genomics. 2000;65:166–73.
57. Yamamoto S, Oka S, Inoue M, Shimuta M, Manabe T, Takahashi H, Miyamoto M, Asano M, Sakagami J, Sudo K, et al. Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning. J Biol Chem. 2002;277:27227–31.
58. Chang C, Rodriguez A, Carretero M, Lopez-Botet M, Phillips JH, Lanier LL. Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Immunol. 1995;25:2433–7.
59. Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG. Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J Exp Med. 1998;187:813–8.
60. Braud VM, Allan DS, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998;391:795–9.
61. Lee N, Llano M, Carretero M, Ishitani A, Navarro F, Lopez-Botet M, Geraghty DE. HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA. 1998;95:5199–204.
62. Vandenbark GR, deCastro CM, Taylor H, Dew-Knight S, Kaufman RE. Cloning and structural analysis of the human c-kit gene. Oncogene. 1992;7:1259–66.
63. Matos ME, Schnier GS, Beecher MS, Ashman LK, William DE, Caligiuri MA. Expression of a functional c-kit receptor on a subset of natural killer cells. J Exp Med. 1993;178:1079–84.
64. Carson WE, Haldar S, Baiocchi RA, Croce CM, Caligiuri MA. The c-kit ligand suppresses apoptosis of human natural killer cells through the upregulation of bcl-2. Proc Natl Acad Sci USA. 1994;91:7553–7.
65. Carson WE, Fehniger TA, Caligiuri MA. CD56bright natural killer cell subsets: characterization of distinct functional responses to interleukin-2 and the c-kit ligand. Eur J Immunol. 1997;27:354–60.
66. Benson DM Jr, Yu J, Becknell B, Wei M, Freud AG, Ferketich AK, Trotta R, Perrotti D, Briesewitz R, Caligiuri MA. Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells. Blood. 2009;113:2706–14.
67. Fehniger TA, Carson WE, Mrozek E, Caligiuri MA. Stem cell factor enhances interleukin-2-mediated expansion of murine natural killer cells in vivo. Blood. 1997;90:3647–53.
68. Di Santo JP, Rodewald HR. In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development. Curr Opin Immunol. 1998;10:196–207.
69. Tsudo M, Kitamura F, Miyasaka M. Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. Proc Natl Acad Sci USA. 1989;86:1982–6.
70. Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol. 2006;6:595–601.
71. Carson WE, Fehniger TA, Haldar S, Eckhert K, Lindemann MJ, Lai CF, Croce CM, Baumann H, Caligiuri MA. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Investig. 1997;99:937–43.
72. Colonna M, Samaridis J. Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science. 1995;268:405–8.
73. Wagtmann N, Biassoni R, Cantoni C, Verdiani S, Malnati MS, Vitale M, Bottino C, Moretta L, Moretta A, Long EO. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity. 1995;2:439–49.
74. D’Andrea A, Chang C, Franz-Bacon K, McClanahan T, Phillips JH, Lanier LL. Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes. J Immunol. 1995;155:2306–10.
75. Pende D, Biassoni R, Cantoni C, Verdiani S, Falco M, di Donato C, Accame L, Bottino C, Moretta A, Moretta L. 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. 1996;184:505–18.
76. Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, Kitamura T, Nicholl J, Sutherland GR, Lanier LL, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996;4:573–81.
77. Shibuya K, Lanier LL, Phillips JH, Ochs HD, Shimizu K, Nakayama E, Nakauchi H, Shibuya A. Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity. 1999;11:615–23.
78. Bottino C, Castriconi R, Pende D, Rivera P, Nanni M, Carnemolla B, Cantoni C, Grassi J, Marcenaro S, Reymond N, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003;198:557–67.
79. Iguchi-Manaka A, Kai H, Yamashita Y, Shibata K, Tahara-Hanaoka S, Honda S, Yasui T, Kikutani H, Shibuya K, Shibuya A. Accelerated tumor growth in mice deficient in DNAM-1 receptor. J Exp Med. 2008;205:2959–64.
80. Chan CJ, Andrews DM, McLaughlin NM, Yagita H, Gilfillan S, Colonna M, Smyth MJ. DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. J Immunol. 2010;184:902–11.
81. Pende D, Castriconi R, Romagnani P, Spaggiari GM, Marcenaro S, Dondero A, Lazzeri E, Lasagni L, Martini S, Rivera P, et al. Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction. Blood. 2006;107:2030–6.
82. Hou S, Ge K, Zheng X, Wei H, Sun R, Tian Z. CD226 protein is involved in immune synapse formation and triggers natural killer (NK) cell activation via its first extracellular domain. J Biol Chem. 2014;289:6969–77.
83. Hou S, Zheng X, Wei H, Tian Z, Sun R. Recombinant soluble CD226 protein directly inhibits cancer cell proliferation in vitro. Int Immunopharmacol. 2014;19:119–26.
84. Boles KS, Nakajima H, Colonna M, Chuang SS, Stepp SE, Bennett M, Kumar V, Mathew PA. Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4. Tissue Antigens. 1999;54:27–34.
85. Brown MH, Boles K, van der Merwe PA, Kumar V, Mathew PA, Barclay AN. 2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48. J Exp Med. 1998;188:2083–90.
86. Bryceson YT, March ME, Ljunggren HG, Long EO. Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood. 2006;107:159–66.
87. Houchins JP, Yabe T, McSherry C, Bach FH. DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J Exp Med. 1991;173:1017–20.
88. Yabe T, McSherry C, Bach FH, Fisch P, Schall RP, Sondel PM, Houchins JP. A multigene family on human chromosome 12 encodes natural killer-cell lectins. Immunogenetics. 1993;37:455–60.
89. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727–9.
90. Raulet DH, Gasser S, Gowen BG, Deng W, Jung H. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol. 2013;31:413–41.
91. Ullrich E, Koch J, Cerwenka A, Steinle A. New prospects on the NKG2D/NKG2DL system for oncology. Oncoimmunology. 2013;2:e26097.
92. Lopez-Soto A, Huergo-Zapico L, Acebes-Huerta A, Villa-Alvarez M, Gonzalez S. NKG2D signaling in cancer immunosurveillance. Int J Cancer. 2015;136:1741–50.
93. Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L, Biassoni R, Moretta A. Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J Exp Med. 1998;188:953–60.
94. Gazit R, Gruda R, Elboim M, Arnon TI, Katz G, Achdout H, Hanna J, Qimron U, Landau G, Greenbaum E, et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat Immunol. 2006;7:517–23.
95. Hudspeth K, Silva-Santos B, Mavilio D. Natural cytotoxicity receptors: broader expression patterns and functions in innate and adaptive immune cells. Front Immunol. 2013;4:69.
96. Thoren FB, Riise RE, Ousback J, Della Chiesa M, Alsterholm M, Marcenaro E, Pesce S, Prato C, Cantoni C, Bylund J, et al. Human NK Cells induce neutrophil apoptosis via an NKp46- and Fas-dependent mechanism. J Immunol. 2012;188:1668–74.
97. Podack ER, Lowrey DM, Lichtenheld M, Olsen KJ, Aebischer T, Binder D, Rupp F, Hengartner H. Structure, function and expression of murine and human perforin 1 (P1). Immunol Rev. 1988;103:203–11.
98. Shinkai Y, Takio K, Okumura K. Homology of perforin to the ninth component of complement (C9). Nature. 1988;334:525–7.
99. Voskoboinik I, Trapani JA. Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function. Front Immunol. 2013;4:441.