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NK cells and their receptors in immune regulation – possible targets for immunomodulation
Název práce v češtině: NK buňky a jejich receptory v imunitní regulaci - možné cíle pro imunomodulaci
Název v anglickém jazyce: NK cells and their receptors in immune regulation – possible targets for immunomodulation
Klíčová slova: Imunomodulace, NK buňky, receptory, cytotoxicita, efektorová funkce, průtoková cytometrie
Klíčová slova anglicky: Immunomodulation, NK cells, receptors, cytotoxicity, effector function, flow cytometry
Akademický rok vypsání: 2012/2013
Typ práce: disertační práce
Jazyk práce: angličtina
Ústav: Akademie věd ČR (11-00048)
Vedoucí / školitel: MUDr. Anna Fišerová, CSc.
Řešitel: skrytý - zadáno a potvrzeno stud. odd.
Datum přihlášení: 27.02.2009
Datum zadání: 27.02.2009
Datum a čas obhajoby: 16.09.2013 10:00
Místo konání obhajoby: Fyziologický ústav AV ČR, v.v.i.
Datum odevzdání elektronické podoby:23.05.2013
Datum proběhlé obhajoby: 16.09.2013
Předmět: Obhajoba dizertační práce (B90002)
Oponenti: doc. RNDr. Jana Pěknicová, CSc.
  doc. RNDr. Zuzana Kročová, Ph.D.
Seznam odborné literatury
List of references

1. Marcenaro, E., S. Carlomagno, S. Pesce, M. Della Chiesa, S. Parolini, A. Moretta, and S. Sivori. 2011. NK cells and their receptors during viral infections. Immunotherapy-Uk. 3:1075-1086.
2. Waldhauer, I., and A. Steinle. 2008. NK cells and cancer immunosurveillance. Oncogene. 27:5932-5943.
3. Gerosa, F., B. Baldani-Guerra, C. Nisii, V. Marchesini, G. Carra, and G. Trinchieri. 2002. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med. 195:327-333.
4. Adam, C., S. King, T. Allgeier, H. Braumuller, C. Luking, J. Mysliwietz, A. Kriegeskorte, D. H. Busch, M. Rocken, and R. Mocikat. 2005. DC-NK cell cross talk as a novel CD4+ T-cell-independent pathway for antitumor CTL induction. Blood. 106:338-344.
5. Malhotra, A., and A. Shanker. 2011. NK cells: immune cross-talk and therapeutic implications. Immunotherapy-Uk. 3:1143-1166.
6. Trinchieri, G. 1989. Biology of Natural-Killer Cells. Advances in Immunology. 47:187-376.
7. Amigorena, S., C. Bonnerot, W. H. Fridman, and J. L. Teillaud. 1990. Recombinant interleukin 2-activated natural killer cells regulate IgG2a production. Eur J Immunol. 20:1781-1787.
8. Koh, C. Y., and D. Yuan. 2000. The functional relevance of NK-cell-mediated upregulation of antigen-specific IgG2a responses. Cell Immunol. 204:135-142.
9. Hinds, L. B. D., M. S. Alexandre-Moreira, D. Decote-Ricardo, M. P. Nunes, and L. M. T. Pecanha. 2001. Increased immunoglobulin secretion by B lymphocytes from Trypanosoma cruzi infected mice after B lymphocytes-natural killer cell interaction. Parasite Immunol. 23:581-586.
10. Lunemann, A., J. D. Lunemann, and C. Munz. 2009. Regulatory NK-cell functions in inflammation and autoimmunity. Mol Med. 15:352-358.
11. Perricone, R., C. Perricone, C. De Carolis, and Y. Shoenfeld. 2008. NK cells in autoimmunity: a two-edg'd weapon of the immune system. Autoimmun Rev. 7:384-390.
12. Moffett-King, A. 2002. Natural killer cells and pregnancy. Nat Rev Immunol. 2:656-663.
13. Gill, R. G. 2010. NK cells: elusive participants in transplantation immunity and tolerance. Curr Opin Immunol. 22:649-654.
14. Horowitz, A., K. A. Stegmann, and E. M. Riley. 2011. Activation of natural killer cells during microbial infections. Front Immunol. 2:88.
15. Wilk, E., K. Kalippke, S. Buyny, R. E. Schmidt, and R. Jacobs. 2008. New aspects of NK cell subset identification and inference of NK cells' regulatory capacity by assessing functional and genomic profiles. Immunobiology. 213:271-283.
16. Wendt, K., E. Wilk, S. Buyny, J. Buer, R. E. Schmidt, and R. Jacobs. 2006. Gene and protein characteristics reflect functional diversity of CD56(dim) and CD56(bright) NK cells. J Leukocyte Biol. 80:1529-1541.
17. Hayakawa, Y., and M. J. Smyth. 2006. CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. Journal of Immunology. 176:1517-1524.
18. Hayakawa, Y., N. D. Huntington, S. L. Nutt, and M. J. Smyth. 2006. Functional subsets of mouse natural killer cells. Immunol Rev. 214:47-55.
19. Walzer, T., M. Blery, J. Chaix, N. Fuseri, L. Chasson, S. H. Robbins, S. Jaeger, P. Andre, L. Gauthier, L. Daniel, K. Chemin, Y. Morel, M. Dalod, J. Imbert, M. Pierres, A. Moretta, F. Romagne, and E. Vivier. 2007. Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46. Proc Natl Acad Sci U S A. 104:3384-3389.
20. Carlyle, J. R., A. Mesci, B. Ljutic, S. Belanger, L. H. Tai, E. Rousselle, A. D. Troke, M. F. Proteau, and A. P. Makrigiannis. 2006. Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells. Journal of Immunology. 176:7511-7524.
21. Moretta, L., R. Biassoni, C. Bottino, M. C. Mingari, and A. Moretta. 2000. Human NK-cell receptors. Immunol Today. 21:420-422.
22. Chambers, W. H., and C. S. Brissettestorkus. 1995. Hanging in the Balance - Natural-Killer-Cell Recognition of Target-Cells. Chem Biol. 2:429-435.
23. Lanier, L. L. 2001. On guard - activating NK cell receptors. Nat Immunol. 2:23-27.
24. Blery, M., L. Olcese, and E. Vivier. 2000. Early signaling via inhibitory and activating NK receptors. Hum Immunol. 61:51-64.
25. Ravetch, J. V., and L. L. Lanier. 2000. Immune inhibitory receptors. Science. 290:84-89.
26. Ljunggren, H. G., and K. Karre. 1990. In Search of the Missing Self - Mhc Molecules and Nk Cell Recognition. Immunol Today. 11:237-244.
27. Garrido, F., F. Ruiz-Cabello, T. Cabrera, J. J. Perez-Villar, M. Lopez-Botet, M. Duggan-Keen, and P. L. Stern. 1997. Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today. 18:89-95.
28. Moretta, L., R. Biassoni, C. Bottino, C. Cantoni, D. Pende, M. C. Mingari, and A. Moretta. 2002. Human NK cells and their receptors. Microbes Infect. 4:1539-1544.
29. Isakov, N. 1998. Role of immunoreceptor tyrosine-based activation motif in signal transduction from antigen and Fc receptors. Adv Immunol. 69:183-247.
30. Lanier, L. L., G. Yu, and J. H. Phillips. 1991. Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation. J Immunol. 146:1571-1576.
31. Wu, J., H. Cherwinski, T. Spies, J. H. Phillips, and L. L. Lanier. 2000. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J Exp Med. 192:1059-1068.
32. Perussia, B. 2000. Signaling for cytotoxicity. Nat Immunol. 1:372-374.
33. Anegon, I., M. C. Cuturi, G. Trinchieri, and B. Perussia. 1988. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med. 167:452-472.
34. Azzoni, L., I. Anegon, B. Calabretta, and B. Perussia. 1995. Ligand binding to Fc gamma R induces c-myc-dependent apoptosis in IL-2-stimulated NK cells. J Immunol. 154:491-499.
35. Takai, T., M. Li, D. Sylvestre, R. Clynes, and J. V. Ravetch. 1994. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 76:519-529.
36. Clynes, R. A., T. L. Towers, L. G. Presta, and J. V. Ravetch. 2000. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med. 6:443-446.
37. Jiang, K., B. Zhong, D. L. Gilvary, B. C. Corliss, E. Hong-Geller, S. Wei, and J. Y. Djeu. 2000. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Nat Immunol. 1:419-425.
38. Wu, J., Y. Song, A. B. Bakker, S. Bauer, T. Spies, L. L. Lanier, and J. H. Phillips. 1999. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 285:730-732.
39. Bauer, S., V. Groh, J. Wu, A. Steinle, J. H. Phillips, L. L. Lanier, and T. Spies. 1999. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 285:727-729.
40. Ingley, E. 2008. Src family kinases: regulation of their activities, levels and identification of new pathways. Biochim Biophys Acta. 1784:56-65.
41. Tourdot, B. E., M. K. Brenner, K. C. Keough, T. Holyst, P. J. Newman, and D. K. Newman. 2013. Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM)-Mediated Inhibitory Signaling Is Regulated by Sequential Phosphorylation Mediated by Distinct Nonreceptor Tyrosine Kinases: A Case Study Involving PECAM-1. Biochemistry-Us. 52:2597-2608.
42. Lowell, C. A. 2011. Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk. Cold Spring Harb Perspect Biol. 3.
43. Lanier, L. L. 1998. NK cell receptors. Annu Rev Immunol. 16:359-393.
44. Ortaldo, J. R., L. H. Mason, T. A. Gregorio, J. Stoll, and R. T. Winkler-Pickett. 1997. The Ly-49 family: regulation of cytokine production in murine NK cells. J Leukoc Biol. 62:381-388.
45. Leibson, P. J. 1997. Signal transduction during natural killer cell activation: inside the mind of a killer. Immunity. 6:655-661.
46. Vivier, E., and M. Daeron. 1997. Immunoreceptor tyrosine-based inhibition motifs. Immunol Today. 18:286-291.
47. Valiante, N. M., J. H. Phillips, L. L. Lanier, and P. Parham. 1996. Killer cell inhibitory receptor recognition of human leukocyte antigen (HLA) class I blocks formation of a pp36/PLC-gamma signaling complex in human natural killer (NK) cells. J Exp Med. 184:2243-2250.
48. Brumbaugh, K. M., J. J. Perez-Villar, C. J. Dick, R. A. Schoon, M. Lopez-Botet, and P. J. Leibson. 1996. Clonotypic differences in signaling from CD94 (kp43) on NK cells lead to divergent cellular responses. J Immunol. 157:2804-2812.
49. Binstadt, B. A., K. M. Brumbaugh, C. J. Dick, A. M. Scharenberg, B. L. Williams, M. Colonna, L. L. Lanier, J. P. Kinet, R. T. Abraham, and P. J. Leibson. 1996. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Immunity. 5:629-638.
50. Nakamura, M. C., E. C. Niemi, M. J. Fisher, L. D. Shultz, W. E. Seaman, and J. C. Ryan. 1997. Mouse Ly-49A interrupts early signaling events in natural killer cell cytotoxicity and functionally associates with the SHP-1 tyrosine phosphatase. J Exp Med. 185:673-684.
51. Ono, M., S. Bolland, P. Tempst, and J. V. Ravetch. 1996. Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB. Nature. 383:263-266.
52. Gupta, N., A. M. Scharenberg, D. N. Burshtyn, N. Wagtmann, M. N. Lioubin, L. R. Rohrschneider, J. P. Kinet, and E. O. Long. 1997. Negative signaling pathways of the killer cell inhibitory receptor and Fc gamma RIIb1 require distinct phosphatases. J Exp Med. 186:473-478.
53. Mandelboim, O., N. Lieberman, M. Lev, L. Paul, T. I. Arnon, Y. Bushkin, D. M. Davis, J. L. Strominger, J. W. Yewdell, and A. Porgador. 2001. Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature. 409:1055-1060.
54. Bubic, I., M. Wagner, A. Krmpotic, T. Saulig, S. Kim, W. M. Yokoyama, S. Jonjic, and U. H. Koszinowski. 2004. Gain of virulence caused by loss of a gene in murine cytomegalovirus. J Virol. 78:7536-7544.
55. Newman, K. C., and E. M. Riley. 2007. Whatever turns you on: accessory-cell-dependent activation of NK cells by pathogens. Nat Rev Immunol. 7:279-291.
56. Humann, J., and L. L. Lenz. 2010. Activation of Naive NK Cells in Response to Listeria monocytogenes Requires IL-18 and Contact with Infected Dendritic Cells. Journal of Immunology. 184:5172-5178.
57. Lanier, L. L., B. Corliss, and J. H. Phillips. 1997. Arousal and inhibition of human NK cells. Immunol Rev. 155:145-154.
58. Cerwenka, A., J. L. Baron, and L. L. Lanier. 2001. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. P Natl Acad Sci USA. 98:11521-11526.
59. Lanier, L. L. 2005. NK cell recognition. Annual Review of Immunology. 23:225-274.
60. Faure, M., and E. O. Long. 2002. KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. Journal of Immunology. 168:6208-6214.
61. Rajagopalan, S., J. Fu, and E. O. Long. 2001. Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells. Journal of Immunology. 167:1877-1881.
62. Kikuchi-Maki, A., S. Yusa, T. L. Catina, and K. S. Campbell. 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.
63. Chang, C. W., A. Rodriguez, M. Carretero, M. Lopezbotet, J. H. Phillips, and L. L. Lanier. 1995. Molecular Characterization of Human Cd94 - a Type-Ii Membrane Glycoprotein Related to the C-Type Lectin Superfamily. European Journal of Immunology. 25:2433-2437.
64. Vance, R. E., J. R. Kraft, J. D. Altman, P. E. Jensen, and D. H. Raulet. 1998. Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b). Journal of Experimental Medicine. 188:1841-1848.
65. Vance, R. E., A. M. Jamieson, and D. H. Raulet. 1999. Recognition of the class Ib molecule Qa-1(b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells. Journal of Experimental Medicine. 190:1801-1812.
66. Lanier, L. L., B. Corliss, J. Wu, and J. H. Phillips. 1998. Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity. 8:693-701.
67. Carretero, M., C. Cantoni, T. Bellon, C. Bottino, R. Biassoni, A. Rodriguez, J. J. PerezVillar, L. Moretta, A. Moretta, and M. LopezBotet. 1997. The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules. European Journal of Immunology. 27:563-567.
68. Vales-Gomez, M., H. T. Reyburn, R. A. Erskine, M. Lopez-Botet, and J. L. Strominger. 1999. Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94/NKG2-A and the activating receptor CD94/NKG2-C to HLA-E. Embo Journal. 18:4250-4260.
69. Lee, N., D. R. Goodlett, A. Ishitani, H. Marquardt, and D. E. Geraghty. 1998. HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. Journal of Immunology. 160:4951-4960.
70. Ho, E. L., L. N. Carayannopoulos, J. Poursine-Laurent, J. Kinder, B. Plougastel, H. R. C. Smith, and W. M. Yokoyama. 2002. Costimulation of multiple NK cell activation receptors by NKG2D. Journal of Immunology. 169:3667-3675.
71. Houchins, J. P., T. Yabe, C. Mcsherry, and F. H. Bach. 1991. DNA-Sequence Analysis of Nkg2, a Family of Related Cdna Clones Encoding Type-Ii Integral Membrane-Proteins on Human Natural-Killer-Cells. Journal of Experimental Medicine. 173:1017-1020.
72. Lodoen, M., K. Ogasawara, J. A. Hamerman, H. Arase, J. P. Houchins, E. S. Mocarski, and L. L. Lanier. 2003. NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. Journal of Experimental Medicine. 197:1245-1253.
73. Groh, V., J. Wu, C. Yee, and T. Spies. 2002. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 419:734-738.
74. Kim, J. Y., Y. O. Son, S. W. Park, J. H. Bae, J. S. Chung, H. H. Kim, B. S. Chung, S. H. Kim, and C. D. Kang. 2006. Increase of NKAG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation. Exp Mol Med. 38:474-484.
75. Galazka, G., A. Jurewicz, W. Orlowski, M. Stasiolek, C. F. Brosnan, C. S. Raine, and K. Selmaj. 2007. EAE tolerance induction with Hsp70-peptide complexes depends on H60 and NKG2D activity. Journal of Immunology. 179:4503-4512.
76. Groh, V., A. Bruhl, H. El-Gabalawy, J. L. Nelson, and T. Spies. 2003. Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rhe'umatoid arthritis. P Natl Acad Sci USA. 100:9452-9457.
77. Plougastel, B., C. Dubbelde, and W. M. Yokoyama. 2001. Cloning of Clr, a new family of lectin-like genes localized between mouse NKrp1a and Cd69. Immunogenetics. 53:209-214.
78. Carlyle, J. R., A. M. Jamieson, S. Gasser, C. S. Clingan, H. Arase, and D. H. Raulet. 2004. Missing self-recognition of Ocil/Cir-b by inhibitory NKR-P1 natural killer cell receptors. P Natl Acad Sci USA. 101:3527-3532.
79. Iizuka, K., O. V. Naidenko, B. F. M. Plougastel, D. H. Fremont, and W. M. Yokoyama. 2003. Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors. Nat Immunol. 4:801-807.
80. Rosen, D. B., J. Bettadapura, M. Alsharifi, P. A. Mathew, H. S. Warren, and L. L. Lanier. 2005. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol. 175:7796-7799.
81. Kamishikiryo, J., H. Fukuhara, Y. Okabe, K. Kuroki, and K. Maenaka. 2011. Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1). Journal of Biological Chemistry. 286:23823-23830.
82. Ryan, J. C., E. C. Niemi, M. C. Nakamura, and W. E. Seaman. 1995. NKR-P1A is a target-specific receptor that activates natural killer cell cytotoxicity. J Exp Med. 181:1911-1915.
83. Kumar, V., and A. Sharma. 2009. Adenosine: An endogenous modulator of innate immune system with therapeutic potential. Eur J Pharmacol. 616:7-15.
84. Raskovalova, T., X. J. Huang, M. Sitkovsky, L. C. Zacharia, E. K. Jackson, and E. Gorelik. 2005. G(S) protein-coupled adenosine receptor signaling and lytic function of activated NK cells. Journal of Immunology. 175:4383-4391.
85. Harish, A., G. Hohana, P. Fishman, O. Arnon, and S. Bar-Yehuda. 2003. A3 adenosine receptor agonist potentiates natural killer cell activity. International Journal of Oncology. 23:1245-1249.
86. Vivier, E., and S. Ugolini. 2011. Natural killer cells: from basic research to treatments. Front Immunol. 2:18.
87. Buskas, T., P. Thompson, and G. J. Boons. 2009. Immunotherapy for cancer: synthetic carbohydrate-based vaccines. Chem Commun.5335-5349.
88. Astronomo, R. D., and D. R. Burton. 2010. Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat Rev Drug Discov. 9:308-324.
89. Li, M., L. J. Song, and X. Y. Qin. 2010. Glycan changes: cancer metastasis and anti-cancer vaccines. J Biosciences. 35:665-673.
90. Yin, Z., M. Comellas-Aragones, S. Chowdhury, P. Bentley, K. Kaczanowska, L. Benmohamed, J. C. Gildersleeve, M. G. Finn, and X. Huang. 2013. Boosting Immunity to Small Tumor-Associated Carbohydrates with Bacteriophage Qbeta Capsids. ACS Chem Biol.
91. Huang, Y. L., J. T. Hung, S. K. Cheung, H. Y. Lee, K. C. Chu, S. T. Li, Y. C. Lin, C. T. Ren, T. J. Cheng, T. L. Hsu, A. L. Yu, C. Y. Wu, and C. H. Wong. 2013. Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer. Proc Natl Acad Sci U S A. 110:2517-2522.
92. Gening, M. L., Y. E. Tsvetkov, G. B. Pier, and N. E. Nifantiev. 2007. Synthesis of beta-(1 -> 6)-linked glucosamine oligosaccharides corresponding to fragments of the bacterial surface polysaccharide poly-N-acetylglucosamine. Carbohyd Res. 342:567-575.
93. Lindhorst, T. K., and C. Kieburg. 1996. Glycocoating of oligovalent amines: Synthesis of thiourea-bridged cluster glycosides from glycosyl isothiocyanates. Angewandte Chemie-International Edition in English. 35:1953-1956.
94. Zhang, H. L., Y. Ma, and X. L. Sun. 2010. Recent Developments in Carbohydrate-Decorated Targeted Drug/Gene Delivery. Med Res Rev. 30:270-289.
95. Bernardi, A., J. Jimenez-Barbero, A. Casnati, C. De Castro, T. Darbre, F. Fieschi, J. Finne, H. Funken, K. E. Jaeger, M. Lahmann, T. K. Lindhorst, M. Marradi, P. Messner, A. Molinaro, P. V. Murphy, C. Nativi, S. Oscarson, S. Penades, F. Peri, R. J. Pieters, O. Renaudet, J. L. Reymond, B. Richichi, J. Rojo, F. Sansone, C. Schaffer, W. B. Turnbull, T. Velasco-Torrijos, S. Vidal, S. Vincent, T. Wennekes, H. Zuilhof, and A. Imberty. 2013. Multivalent glycoconjugates as anti-pathogenic agents. Chem Soc Rev. 42:4709-4727.
96. Sutlu, T., and E. Alici. 2009. Natural killer cell-based immunotherapy in cancer: current insights and future prospects. J Intern Med. 266:154-181.
97. Konjevic, G., V. Jurisic, V. Jovic, A. Vuletic, K. Mirjacic Martinovic, S. Radenkovic, and I. Spuzic. 2012. Investigation of NK cell function and their modulation in different malignancies. Immunol Res. 52:139-156.
98. Azzoni, L., O. Zatsepina, B. Abebe, I. M. Bennett, P. Kanakaraj, and B. Perussia. 1998. Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells. J Immunol. 161:3493-3500.
99. Delves, P. J. 1998. The role of glycosylation in autoimmune disease. Autoimmunity. 27:239-253.
100. Park, Y. W., S. J. Kee, Y. N. Cho, E. H. Lee, H. Y. Lee, E. M. Kim, M. H. Shin, J. J. Park, T. J. Kim, S. S. Lee, D. H. Yoo, and H. S. Kang. 2009. Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Arthritis Rheum. 60:1753-1763.
101. Aust, J. G., F. Gays, K. M. Mickiewicz, E. Buchanan, and C. G. Brooks. 2009. The Expression and Function of the NKRP1 Receptor Family in C57BL/6 Mice. Journal of Immunology. 183:106-116.
102. Lanier, L. L., C. W. Chang, and J. H. Phillips. 1994. Human Nkr-P1a - a Disulfide-Linked Homodimer of the C-Type Lectin Superfamily Expressed by a Subset of Nk and T-Lymphocytes. Journal of Immunology. 153:2417-2428.
103. Poggi, A., P. Costa, L. Morelli, C. Cantoni, N. Pella, F. Spada, R. Biassoni, L. Nanni, V. Revello, E. Tomasello, M. C. Mingari, A. Moretta, and L. Moretta. 1996. Expression of human NKRP1A by CD34(+) immature thymocytes: NKRP1A-mediated regulation of proliferation and cytolytic activity. European Journal of Immunology. 26:1266-1272.
104. Exley, M., S. Porcelli, M. Furman, J. Garcia, and S. Balk. 1998. CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24J alpha Q T cell receptor alpha chains. Journal of Experimental Medicine. 188:867-876.
105. Richter, J., V. Benson, V. Grobarova, J. Svoboda, J. Vencovsky, R. Svobodova, and A. Fiserova. 2010. CD161 receptor participates in both impairing NK cell cytotoxicity and the response to glycans and vimentin in patients with rheumatoid arthritis. Clin Immunol. 136:139-147.
106. Ljutic, B., J. R. Carlyle, D. Filipp, R. Nakagawa, M. Julius, and J. C. Zuniga-Pflucker. 2005. Functional requirements for signaling through the stimulatory and inhibitory mouse NKR-P1 (CD161) NK cell receptors. J Immunol. 174:4789-4796.
107. Koo, G. C., and J. R. Peppard. 1984. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 3:301-303.
108. Ryan, J. C., J. Turck, E. C. Niemi, W. M. Yokoyama, and W. E. Seaman. 1992. Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules. J Immunol. 149:1631-1635.
109. Carlyle, J. R., A. Martin, A. Mehra, L. Attisano, F. W. Tsui, and J. C. Zuniga-Pflucker. 1999. Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function. J Immunol. 162:5917-5923.
110. Vannucci, L., A. Fiserova, K. Sadalapure, T. K. Lindhorst, M. Kuldova, P. Rossmann, O. Horvath, V. Kren, P. Krist, K. Bezouska, M. Luptovcova, F. Mosca, and M. Pospisil. 2003. Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo. Int J Oncol. 23:285-296.
111. Snapper, C. M., H. Yamaguchi, M. A. Moorman, R. Sneed, D. Smoot, and J. J. Mond. 1993. Natural killer cells induce activated murine B cells to secrete Ig. J Immunol. 151:5251-5260.
112. Hulikova, K., V. Benson, J. Svoboda, P. Sima, and A. Fiserova. 2009. N-Acetyl-D-glucosamine-coated polyamidoamine dendrimer modulates antibody formation via natural killer cell activation. Int Immunopharmacol. 9:792-799.
113. Wilder, J. A., C. Y. Koh, and D. Yuan. 1996. The role of NK cells during in vivo antigen-specific antibody responses. Journal of Immunology. 156:146-152.
114. Caputo, M., M. Nicotra, and E. Gloria-Bottini. 2008. Fertility transition: forecast for demography. Hum Biol. 80:359-376.
115. Giuliani, A., W. Schoell, J. Auner, and W. Urdl. 1998. Controlled ovarian hyperstimulation in assisted reproduction: effect on the immune system. Fertil Steril. 70:831-835.
116. Karami, N., M. G. Boroujerdnia, R. Nikbakht, and A. Khodadadi. 2012. Enhancement of peripheral blood CD56(dim) cell and NK cell cytotoxicity in women with recurrent spontaneous abortion or in vitro fertilization failure. J Reprod Immunol. 95:87-92.
117. Sacks, G., Y. Yang, E. Gowen, S. Smith, L. Fay, and M. Chapman. 2012. Detailed analysis of peripheral blood natural killer cells in women with repeated IVF failure. Am J Reprod Immunol. 67:434-442.
118. Hunt, J. S., and D. L. Langat. 2009. HLA-G: a human pregnancy-related immunomodulator. Curr Opin Pharmacol. 9:462-469.
119. Hunt, J. S., M. G. Petroff, R. H. McIntire, and C. Ober. 2005. HLA-G and immune tolerance in pregnancy. FASEB J. 19:681-693.
120. Middleton, D., and F. Gonzelez. 2010. The extensive polymorphism of KIR genes. Immunology. 129:8-19.
121. Miah, S. M., T. L. Hughes, and K. S. Campbell. 2008. KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules. J Immunol. 180:2922-2932.
122. Brown, D., J. Trowsdale, and R. Allen. 2004. The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens. 64:215-225.
123. Moysey, R. K., Y. Li, S. J. Paston, E. E. Baston, M. S. Sami, B. J. Cameron, J. Gavarret, P. Todorov, A. Vuidepot, S. M. Dunn, N. J. Pumphrey, K. J. Adams, F. Yuan, R. E. Dennis, D. H. Sutton, A. D. Johnson, J. E. Brewer, R. Ashfield, N. M. Lissin, and B. K. Jakobsen. 2010. High affinity soluble ILT2 receptor: a potent inhibitor of CD8(+) T cell activation. Protein Cell. 1:1118-1127.
124. De Maria, A., F. Bozzano, C. Cantoni, and L. Moretta. 2011. Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A. 108:728-732.
125. Saito, S., K. Nishikawa, T. Morii, M. Enomoto, N. Narita, K. Motoyoshi, and M. Ichijo. 1993. Cytokine production by CD16-CD56bright natural killer cells in the human early pregnancy decidua. Int Immunol. 5:559-563.
126. Chaouat, G., S. Dubanchet, and N. Ledee. 2007. Cytokines: Important for implantation? J Assist Reprod Genet. 24:491-505.
127. Lachapelle, M. H., R. Hemmings, D. C. Roy, T. Falcone, and P. Miron. 1996. Flow cytometric evaluation of leukocyte subpopulations in the follicular fluids of infertile patients. Fertil Steril. 65:1135-1140.
128. Lukassen, H. G., A. van der Meer, M. J. van Lierop, E. J. Lindeman, I. Joosten, and D. D. Braat. 2003. The proportion of follicular fluid CD16+CD56DIM NK cells is increased in IVF patients with idiopathic infertility. J Reprod Immunol. 60:71-84.
129. Fredholm, B. B., I. J. AP, K. A. Jacobson, K. N. Klotz, and J. Linden. 2001. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev. 53:527-552.
130. Ohta, A., and M. Sitkovsky. 2001. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 414:916-920.
131. Lokshin, A., T. Raskovalova, X. Huang, L. C. Zacharia, E. K. Jackson, and E. Gorelik. 2006. Adenosine-mediated inhibition of the cytotoxic activity and cytokine production by activated natural killer cells. Cancer Res. 66:7758-7765.
132. Atanackovic, D., A. Nierhaus, M. Neumeier, D. K. Hossfeld, and S. Hegewisch-Becker. 2002. 41.8 degrees C whole body hyperthermia as an adjunct to chemotherapy induces prolonged T cell activation in patients with various malignant diseases. Cancer Immunol Immunother. 51:603-613.
133. Milani, V., and E. Noessner. 2006. Effects of thermal stress on tumor antigenicity and recognition by immune effector cells. Cancer Immunol Immun. 55:312-319.
134. Shen, R. N., L. Lu, P. Young, H. Shidnia, N. B. Hornback, and H. E. Broxmeyer. 1994. Influence of elevated temperature on natural killer cell activity, lymphokine-activated killer cell activity and lectin-dependent cytotoxicity of human umbilical cord blood and adult blood cells. Int J Radiat Oncol Biol Phys. 29:821-826.
135. Vartak, S., K. C. George, and B. B. Singh. 1996. Antitumor effect of pre-transplantation local hyperthermia and augmentation by dietary unsaturated fat. Indian J Exp Biol. 34:825-832.
136. Szmigielski, S., J. Sobczynski, G. Sokolska, B. Stawarz, H. Zielinski, and Z. Petrovich. 1991. Effects of local prostatic hyperthermia on human NK and T cell function. Int J Hyperthermia. 7:869-880.
137. Ostapenko, V. V., H. Tanaka, M. Miyano, T. Nishide, H. Ueda, I. Nishide, Y. Tanaka, M. Mune, and S. Yukawa. 2005. Immune-related effects of local hyperthermia in patients with primary liver cancer. Hepatogastroenterology. 52:1502-1506.
138. Stawarz, B., H. Zielinski, S. Szmigielski, E. Rappaport, P. Debicki, and Z. Petrovich. 1993. Transrectal hyperthermia as palliative treatment for advanced adenocarcinoma of prostate and studies of cell-mediated immunity. Urology. 41:548-553.
139. Porch, A., D. Slocombe, and P. P. Edwards. 2013. Microwave absorption in powders of small conducting particles for heating applications. Phys Chem Chem Phys. 15:2757-2763.
140. Kateb, B., K. Chiu, K. L. Black, V. Yamamoto, B. Khalsa, J. Y. Ljubimova, H. Ding, R. Patil, J. A. Portilla-Arias, M. Modo, D. F. Moore, K. Farahani, M. S. Okun, N. Prakash, J. Neman, D. Ahdoot, W. Grundfest, S. Nikzad, and J. D. Heiss. 2011. Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? Neuroimage. 54 Suppl 1:S106-124.
141. Armstead, A. L., and B. Li. 2011. Nanomedicine as an emerging approach against intracellular pathogens. Int J Nanomedicine. 6:3281-3293.
142. Dominguez-Vera, J. M., B. Fernandez, and N. Galvez. 2010. Native and synthetic ferritins for nanobiomedical applications: recent advances and new perspectives. Future Med Chem. 2:609-618.
143. Jain, R. K. 2001. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev. 46:149-168.
144. Watt, R. K. 2011. The many faces of the octahedral ferritin protein. Biometals. 24:489-500.
145. Lin, X., J. Xie, G. Niu, F. Zhang, H. Gao, M. Yang, Q. Quan, M. A. Aronova, G. Zhang, S. Lee, R. Leapman, and X. Chen. 2011. Chimeric ferritin nanocages for multiple function loading and multimodal imaging. Nano Lett. 11:814-819.
146. Bianco, G. A., M. A. Toscano, J. M. Ilarregui, and G. A. Rabinovich. 2006. Impact of protein-glycan interactions in the regulation of autoimmunity and chronic inflammation. Autoimmunity Reviews. 5:349-356.
147. Lengacher, S., C. V. Jongeneel, D. LeRoy, J. D. Lee, V. Kravchenko, R. J. Ulevitch, M. P. Glauser, and D. Heumann. 1996. Reactivity of murine and human recombinant LPS-binding protein (LBP) with LPS and gram negative bacteria. J Inflamm. 47:165-172.
148. Monner, D. A., J. Gmeiner, and P. F. Muhlradt. 1981. Evidence from a Carbohydrate Incorporation Assay for Direct Activation of Bone-Marrow Myelopoietic Precursor Cells by Bacterial-Cell Wall Constitutents. Infection and Immunity. 31:957-964.
149. De Arruda Hinds, L. B., M. S. Alexandre-Moreira, D. Decote-Ricardo, M. P. Nunes, and L. M. Pecanha. 2001. Increased immunoglobulin secretion by B lymphocytes from Trypanosoma cruzi infected mice after B lymphocytes-natural killer cell interaction. Parasite Immunol. 23:581-586.
150. Hulikova, K., J. Svoboda, V. Benson, V. Grobarova, and A. Fiserova. 2011. N-Acetyl-d-glucosamine-coated polyamidoamine dendrimer promotes tumor-specific B cell responses via natural killer cell activation. Int Immunopharmacol.
Předběžná náplň práce
Abstrakt (česky)

Přirození zabíječi - buňky NK hrají důležitou roli v imunitním dohledu a regulaci jednak přímým cytotoxickým působením na infikované, transformované či jinak poškozené buňky, ale také produkcí cytokínů a chemokínů. Výsledná odpověď je dána převahou stimulačních nebo inhibičních signálů, přenášených širokou paletou membránových receptorů. Zabíječské s Ig–příbuzné molekuly KIR2DL4 a LILRB1, které rozpoznávají vlastní HLA–G molekuly během těhotenství stejně jako NKR–P1 receptory lišící se ve funkci a počtu izotypů jsou druhově závislé a redukované v průběhu fylogeneze, zatímco NKG2D, reagující na stresem indukované proteiny a adenozínové receptory (AR) potlačující zánětovou reakci, zůstávají evolučně konzervované.
Cílem této práce bylo studium zapojení NK buněk a jejich receptorů v několika modelech imunitních poruch a u různých savčích druhů, za účelem získání nového náhledu na jejich funkci a možnost imunitní modulace.
Ukázali jsme zde, že výběr druhu ve studiu ovlivnění NK buněčné funkce může být v některých případech kritický. Reakce na glykany, s využitím syntetického GlcNAc terminovaného glykomimetika GN8P, měla protichůdné účinky na NK buněčnou funkci u lidí a C57Bl/6 myší. U lidí byla snížena cytotoxická aktivita NK buněk s vysokou expresí NKR–P1A, zatímco u myší podání GN8P aktivalo NK buňky a B16F10 specifickou tvorbu protilátek IgG2a izotypu, která následně zvýšila na protilátkách závislou cytotoxicitu (ADCC). Tento účinek byl pozorován pouze u myší nesoucích Nkr-p1(T) gen (kódující NK1.1 receptor). Endogenní hormon lidský chorionický gonadotropin (hCG), projevil jako většina hormonů, míru pleiotropie ve svém účinku. Pozorovali jsme posílení CD8 T buněk na úkor Th lymfocytů a zvýšenou expresi KIR2DL4 receptoru na NK buňkách, která podporuje produkci cytokinů. Navíc je tento účinek protichůdný k zamýšlenému užití hCG, tj. zlepšení výsledku postupů asistované reprodukce, protože takový profil byl pozorován u neúspěšných implantací. Evoluční konzervovanost adenozínových receptorů byla ověřena pomocí agonisty A2AAR – CPCA, který měl srovnatelné tlumící účinky na NK buněčnou cytotoxicitu u všech sledovaných savčích druhů (člověk, prase, koza, potkan, myš) u zdravých i nádorových jedinců. Lokální mikrovlnná hypertermie (HT) in vivo do místa nádoru vykázala pozitivní účinek nejen na redukci nádorových buněk, ale také na NK buněčnou cytotoxicitu, přesto že celkové zastoupení NK buněk ve slezině nebylo ovlivněno. Tento postup je však omezen pouze na lokalizované, primární nádory. Pro další optimalizaci HT byly vyvinuty multifunkční nanočástice založené na lidském feritinu a nádorově specifických cílících struktur. Tato nanoplatforma může zvýšit efektivitu HT terapie i na cirkulující nádorové buňky nebo metastatická ložiska.
Naše výsledky prokázaly klíčové zapojení NK buněk v rozvoji a regulaci imunitní odpovědi v průběhu autoimunitních a reprodukčních poruch, nádorové transformaci nebo teplotního šoku. Tato práce přináší nové možnosti imunitní modulace prostřednictvím NK buněk, ale další výzkum je nutný k jejich plnému využití.
Zde poskytujeme základy k těmto výzkumům a následně možným budoucím klinickým aplikacím. V dalším studiu bude perspektivní sledovat vliv hormonálních hladin nebo autoimunitních změn u myších kmenů v závislosti na NKR–P1 a Ly49 fenotypu.
Předběžná náplň práce v anglickém jazyce
Abstract (english)

Natural Killers – NK cells play an important role in immune surveilance and regulation either by direct cytotoxicity towards infected, transformed or otherwise damaged cells, or by production of cytokines and chemokines. The resulting response of NK cells is given by the sum of stimulating and inhibiting signals, tranduced by a wide array of receptors. Killer Ig–like receptors KIR2DL4 and LILRB1, which recognize self HLA–G molecules in pregnancy, as well as NKR–P1 receptors, which differ in the number of isotypes, are species–dependent and reduced during phylogenesis. NKG2D, reacting to stress–inducible proteins, and adenosine receptors (AR), which supress the inflamatory reaction, remain evolutionary conserved.
The aim of this work was to study the involvement of NK cells and their receptors in several immune disorders and in various species, to provide new insights into their function and posisible immune modulation.
We have shown here, that the choice of species in the study of NK cell effector functions may be crucial in some cases. The reaction to glycans, using synthetic GlcNAc–terminated glycomimetics GN8P, exerted opposing effects on NK cell function in humans and C57Bl/6 mice. In humans, the glycomimetic decreased cytotoxic activity of high NKR–P1A expressing NK cells, while in mice it mounted an NK cell–mediated antibody formation and tumor–specific IgG2a production with subsequent increase in antibody dependent cellular cytotoxicity (ADCC). This effect was observed only in C57BL/6 mice expressing Nkr–p1c(T) gene (coding NK1.1 receptor). Endogenous hormone human chorionic gonadotropin (hCG), exerted as most other hormones a degree of pleiotropy in its effect. We observed a preference of cytotoxic over helper T cells and increased KIR2DL4 expression on NK cells, which renders them more prone toward cytokine production. Moreover, this effect proved to be antagonistic to the original intent of the hCG use – that is to improve the outcome of assisted reproduction courses, since such profile was observed during failed embryotransfers. A2A adenosine receptor agonist CPCA on the other hand, was used to prove the evolutionary conserved mechanisms in its function, by thwarting NK cell cytotoxicity in healthy and immunocompromised subjects equally (human, pig, goat, rat, mouse). In vivo tumor–localized hyperthermia (LHT) proved to have beneficial effect on NK cell–mediated lytic activity, despite the NK cell distribution remained unchanged. This procedure is however limited to localized, primary tumors. For further optimization of LHT, multifunctional ferritin–based nanoparticles with tumor targeting structures were developed. This nanoplatform may increase the efficacy of LHT therapy onto circulating cancer cells or metastatic foci.
Our results proved the key involvement of NK cells in the development and regulation of immune response in autoimmune and reproductive disorders, tumor transformation or heat–induced stress. This work brings new options for NK cell–mediated immune modulation, but further research is needed to achieve their full potential. We here provide the basis for this research and its possible clinical applications in the future. It would be perspective in future studies to observe the hormonal levels or autoimmune changes in murine strains with varying NKR–P1 and Ly49 phenotypes.
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