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Cancer Immunology, Immunotherapy

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19.08.2015 | Symposium-in-writing paper

Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance

verfasst von: Angela R. Manser, Markus Uhrberg

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 4/2016

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Abstract

A key feature of human natural killer (NK) cells, which enables efficient recognition of infected and malignant target cells, is the expression of HLA class I-specific receptors of the KIR and NKG2 gene families. Cell-to-cell variability in receptor expression leads to the formation of complex NK cell repertoires. As outlined here, NK cells go through major changes from newborns to adults characterized by downregulation of the inhibitory NKG2A receptor and concomitant upregulation of KIR family members. This process is completed in young adults, and in the majority of individuals, KIR/NKG2A repertoires remain remarkably stable until old age. Nonetheless, age-related factors have the potential to majorly influence the complexity of NK cell repertoires: Firstly infection with HCMV is associated with major clonal expansions of terminally differentiated NKG2C- and KIR-expressing NK cells in certain individuals. Secondly, ineffective hematopoiesis can lead to immature and less diversified NK cell repertoires as observed in myelodysplastic syndrome (MDS), a malignant disease of the elderly. Thus, whereas in the majority of elderly the NK cell compartment appears to be highly stable in terms of function and phenotype, in a minority of subjects a breakdown of NK cell repertoire diversity is observed that might influence immune surveillance and healthy aging.

WHO Globocan (2008) Cancer incidence and mortality worldwide. http://globocan.iarc.fr. Accessed 22 April 2015

Fulop T, Larbi A, Pawelec G (2013) Human T cell aging and the impact of persistent viral infections. Front Immunol 4:271. doi:10.3389/fimmu.2013.00271 CrossRefPubMedPubMedCentral

Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5(2):133–139. doi:10.1038/ni1033 CrossRefPubMed

Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ (2005) The influence of age on T cell generation and TCR diversity. J Immunol 174(11):7446–7452. doi:10.4049/jimmunol.174.11.7446 CrossRefPubMed

Manser AR, Weinhold S, Uhrberg M (2015) Human KIR repertoires: shaped by genetic diversity and evolution. Immunol Rev 267. doi:10.1111/imr.12316

Weng NP (2006) Aging of the immune system: how much can the adaptive immune system adapt? Immunity 24(5):495–499. doi:10.1016/j.immuni.2006.05.001 CrossRefPubMedPubMedCentral

Le Garff-Tavernier M, Beziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debre P, Merle-Beral H, Vieillard V (2010) Human NK cells display major phenotypic and functional changes over the life span. Aging Cell 9(4):527–535. doi:10.1111/j.1474-9726.2010.00584.x CrossRefPubMed

Almeida-Oliveira A, Smith-Carvalho M, Porto LC, Cardoso-Oliveira J, Ribeiro Ados S, Falcao RR, Abdelhay E, Bouzas LF, Thuler LC, Ornellas MH, Diamond HR (2011) Age-related changes in natural killer cell receptors from childhood through old age. Hum Immunol 72(4):319–329. doi:10.1016/j.humimm.2011.01.009 CrossRefPubMed

Hazeldine J, Hampson P, Lord JM (2012) Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell 11(5):751–759. doi:10.1111/j.1474-9726.2012.00839.x CrossRefPubMed

10.

Lutz CT, Karapetyan A, Al-Attar A, Shelton BJ, Holt KJ, Tucker JH, Presnell SR (2011) Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults. J Immunol 186(8):4590–4598. doi:10.4049/jimmunol.1002732 CrossRefPubMedPubMedCentral

11.

Lutz CT, Moore MB, Bradley S, Shelton BJ, Lutgendorf SK (2005) Reciprocal age related change in natural killer cell receptors for MHC class I. Mech Ageing Dev 126(6–7):722–731. doi:10.1016/j.mad.2005.01.004 CrossRefPubMedPubMedCentral

12.

Campos C, Pera A, Sanchez-Correa B, Alonso C, Lopez-Fernandez I, Morgado S, Tarazona R, Solana R (2014) Effect of age and CMV on NK cell subpopulations. Exp Gerontol 54:130–137. doi:10.1016/j.exger.2014.01.008 CrossRefPubMed

13.

Chidrawar SM, Khan N, Chan YL, Nayak L, Moss PA (2006) Ageing is associated with a decline in peripheral blood CD56^bright NK cells. Immun Ageing 3:10. doi:10.1186/1742-4933-3-10 CrossRefPubMedPubMedCentral

14.

Uhrberg M (2005) The CD107 mobilization assay: viable isolation and immunotherapeutic potential of tumor-cytolytic NK cells. Leukemia 19(5):707–709. doi:10.1038/sj.leu.2403705 CrossRefPubMed

15.

Bjorkstrom NK, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson MA, Bjorklund AT, Flodstrom-Tullberg M, Michaelsson J, Rottenberg ME, Guzman CA, Ljunggren HG, Malmberg KJ (2010) Expression patterns of NKG2A, KIR, and CD57 define a process of CD56^dim NK-cell differentiation uncoupled from NK-cell education. Blood 116(19):3853–3864. doi:10.1182/blood-2010-04-281675 CrossRefPubMed

16.

Beziat V, Descours B, Parizot C, Debre P, Vieillard V (2010) NK cell terminal differentiation: correlated stepwise decrease of NKG2A and acquisition of KIRs. PLoS One 5(8):e11966. doi:10.1371/journal.pone.0011966 CrossRefPubMedPubMedCentral

17.

Lopez-Verges S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, Norris PJ, Nixon DF, Lanier LL (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56^dimCD16 + NK-cell subset. Blood 116(19):3865–3874. doi:10.1182/blood-2010-04-282301 CrossRefPubMedPubMedCentral

18.

Juelke K, Killig M, Thiel A, Dong J, Romagnani C (2009) Education of hyporesponsive NK cells by cytokines. Eur J Immunol 39(9):2548–2555. doi:10.1002/eji.200939307 CrossRefPubMed

19.

Campos C, Lopez N, Pera A, Gordillo JJ, Hassouneh F, Tarazona R, Solana R (2015) Expression of NKp30, NKp46 and DNAM-1 activating receptors on resting and IL-2 activated NK cells from healthy donors according to CMV-serostatus and age. Biogerontology. doi:10.1007/s10522-015-9581-0 PubMed

20.

Ferlazzo G, Thomas D, Lin SL, Goodman K, Morandi B, Muller WA, Moretta A, Munz C (2004) The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. J Immunol 172(3):1455–1462. doi:10.4049/jimmunol.172.3.1455 CrossRefPubMed

21.

Nagler A, Lanier LL, Cwirla S, Phillips JH (1989) Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol 143(10):3183–3191PubMed

22.

Hejazi M, Manser AR, Frobel J, Kundgen A, Zhao X, Schonberg K, Germing U, Haas R, Gattermann N, Uhrberg M (2015) Impaired cytotoxicity associated with defective natural killer cell differentiation in myelodysplastic syndromes. Haematologica 100(5):643–652. doi:10.3324/haematol.2014.118679 CrossRefPubMedPubMedCentral

23.

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(10):3146–3151CrossRefPubMed

24.

Romagnani C, Juelke K, Falco M, Morandi B, D’Agostino A, Costa R, Ratto G, Forte G, Carrega P, Lui G, Conte R, Strowig T, Moretta A, Munz C, Thiel A, Moretta L, Ferlazzo G (2007) CD56^brightCD16- killer Ig-like receptor- NK cells display longer telomeres and acquire features of CD56^dim NK cells upon activation. J Immunol 178(8):4947–4955. doi:10.4049/jimmunol.178.8.4947 CrossRefPubMed

25.

Mariani E, Meneghetti A, Formentini I, Neri S, Cattini L, Ravaglia G, Forti P, Facchini A (2003) Different rates of telomere shortening and telomerase activity reduction in CD8 T and CD16 NK lymphocytes with ageing. Exp Gerontol 38(6):653–659. doi:10.1016/S0531-5565(03)00058-5 CrossRefPubMed

26.

Beli E, Duriancik DM, Clinthorne JF, Lee T, Kim S, Gardner EM (2014) Natural killer cell development and maturation in aged mice. Mech Ageing Dev 135:33–40. doi:10.1016/j.mad.2013.11.007 CrossRefPubMedPubMedCentral

27.

Shehata HM, Hoebe K, Chougnet CA (2015) The aged nonhematopoietic environment impairs natural killer cell maturation and function. Aging Cell 14(2):191–199. doi:10.1111/acel.12303 CrossRefPubMedPubMedCentral

28.

Parham P, Norman PJ, Abi-Rached L, Guethlein LA (2012) Human-specific evolution of killer cell immunoglobulin-like receptor recognition of major histocompatibility complex class I molecules. Philos Trans R Soc Lond B Biol Sci 367(1590):800–811. doi:10.1098/rstb.2011.0266 CrossRefPubMedPubMedCentral

29.

Uhrberg M (2005) The KIR gene family: life in the fast lane of evolution. Eur J Immunol 35(1):10–15. doi:10.1002/eji.200425743 CrossRefPubMed

30.

Uhrberg M (2005) Shaping the human NK cell repertoire: an epigenetic glance at KIR gene regulation. Mol Immunol 42(4):471–475. doi:10.1016/j.molimm.2004.07.029 CrossRefPubMed

31.

Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG (1998) 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 187(5):813–818. doi:10.1084/jem.187.5.813 CrossRefPubMedPubMedCentral

32.

Braud VM, Allan DS, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A. B and C. Nature 391(6669):795–799. doi:10.1038/35869 PubMed

33.

Lee N, Llano M, Carretero M, Ishitani A, Navarro F, Lopez-Botet M, Geraghty DE (1998) HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA 95(9):5199–5204. doi:10.1073/pnas.95.9.5199 CrossRefPubMedPubMedCentral

34.

Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285(5428):727–729. doi:10.1126/science.285.5428.727 CrossRefPubMed

35.

Cosman D, Mullberg J, Sutherland CL, Chin W, Armitage R, Fanslow W, Kubin M, Chalupny NJ (2001) ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14(2):123–133. doi:10.1016/S1074-7613(01)00095-4 CrossRefPubMed

36.

Kim S, Poursine-Laurent J, Truscott SM, Lybarger L, Song YJ, Yang L, French AR, Sunwoo JB, Lemieux S, Hansen TH, Yokoyama WM (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436(7051):709–713. doi:10.1038/nature03847 CrossRefPubMed

37.

Fernandez NC, Treiner E, Vance RE, Jamieson AM, Lemieux S, Raulet DH (2005) A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105(11):4416–4423. doi:10.1182/blood-2004-08-3156 CrossRefPubMedPubMedCentral

38.

Anfossi N, Andre P, Guia S, Falk CS, Roetynck S, Stewart CA, Breso V, Frassati C, Reviron D, Middleton D, Romagne F, Ugolini S, Vivier E (2006) Human NK cell education by inhibitory receptors for MHC class I. Immunity 25(2):331–342. doi:10.1016/j.immuni.2006.06.013 CrossRefPubMed

39.

Bienemann K, Iouannidou K, Schoenberg K, Krux F, Reuther S, Feyen O, Bienemann K, Schuster F, Uhrberg M, Laws HJ, Borkhardt A (2011) iNKT cell frequency in peripheral blood of Caucasian children and adolescent: the absolute iNKT cell count is stable from birth to adulthood. Scand J Immunol 74(4):406–411. doi:10.1111/j.1365-3083.2011.02591.x CrossRefPubMed

40.

Schonberg K, Fischer JC, Kogler G, Uhrberg M (2011) Neonatal NK-cell repertoires are functionally, but not structurally, biased toward recognition of self HLA class I. Blood 117(19):5152–5156. doi:10.1182/blood-2011-02-334441 CrossRefPubMed

41.

Schonberg K, Sribar M, Enczmann J, Fischer JC, Uhrberg M (2011) Analyses of HLA-C-specific KIR repertoires in donors with group A and B haplotypes suggest a ligand-instructed model of NK cell receptor acquisition. Blood 117(1):98–107. doi:10.1182/blood-2010-03-273656 CrossRefPubMed

42.

Phillips JH, Lanier LL (1985) A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11 + granular lymphocytes with a natural killer-sensitive tumor cell, K562. J Exp Med 161(6):1464–1482CrossRefPubMed

43.

Nikolich-Zugich J (2008) Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol 8(7):512–522. doi:10.1038/nri2318 CrossRefPubMed

44.

Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E (2012) The impact of CMV infection on survival in older humans. Curr Opin Immunol 24(4):507–511. doi:10.1016/j.coi.2012.04.002 CrossRefPubMed

45.

Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M (2004) Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood 104(12):3664–3671. doi:10.1182/blood-2004-05-2058 CrossRefPubMed

46.

Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296(5571):1323–1326. doi:10.1126/science.1070884 CrossRefPubMed

47.

Beziat V, Liu LL, Malmberg JA, Ivarsson MA, Sohlberg E, Bjorklund AT, Retiere C, Sverremark-Ekstrom E, Traherne J, Ljungman P, Schaffer M, Price DA, Trowsdale J, Michaelsson J, Ljunggren HG, Malmberg KJ (2013) NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs. Blood 121(14):2678–2688. doi:10.1182/blood-2012-10-459545 CrossRefPubMedPubMedCentral

48.

Bjorkstrom NK, Lindgren T, Stoltz M, Fauriat C, Braun M, Evander M, Michaelsson J, Malmberg KJ, Klingstrom J, Ahlm C, Ljunggren HG (2010) Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus. J Exp Med 208(1):13–21. doi:10.1084/jem.20100762 CrossRefPubMed

49.

Beziat V, Dalgard O, Asselah T, Halfon P, Bedossa P, Boudifa A, Hervier B, Theodorou I, Martinot M, Debre P, Bjorkstrom NK, Malmberg KJ, Marcellin P, Vieillard V (2012) CMV drives clonal expansion of NKG2C + NK cells expressing self-specific KIRs in chronic hepatitis patients. Eur J Immunol 42(2):447–457. doi:10.1002/eji.201141826 CrossRefPubMed

50.

Guma M, Cabrera C, Erkizia I, Bofill M, Clotet B, Ruiz L, Lopez-Botet M (2006) Human cytomegalovirus infection is associated with increased proportions of NK cells that express the CD94/NKG2C receptor in aviremic HIV-1-positive patients. J Infect Dis 194(1):38–41. doi:10.1086/504719 CrossRefPubMed

51.

Elmaagacli AH, Steckel NK, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M, Christoph S, Gromke T, Kordelas L, Ottinger HD, Ross RS, Horn PA, Schnittger S, Beelen DW (2011) Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood 118(5):1402–1412. doi:10.1182/blood-2010-08-304121 CrossRefPubMed

52.

Germing U, Aul C, Niemeyer CM, Haas R, Bennett JM (2008) Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes. Ann Hematol 87(9):691–699. doi:10.1007/s00277-008-0499-3 CrossRefPubMed

53.

Geyh S, Oz S, Cadeddu RP, Frobel J, Bruckner B, Kundgen A, Fenk R, Bruns I, Zilkens C, Hermsen D, Gattermann N, Kobbe G, Germing U, Lyko F, Haas R, Schroeder T (2013) Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells. Leukemia 27(9):1841–1851. doi:10.1038/leu.2013.193 CrossRefPubMed

54.

Chiu BC, Martin BE, Stolberg VR, Chensue SW (2013) The host environment is responsible for aging-related functional NK cell deficiency. J Immunol 191(9):4688–4698. doi:10.4049/jimmunol.1301625 CrossRefPubMed

55.

Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356(9244):1795–1799. doi:10.1016/S0140-6736(00)03231-1 CrossRefPubMed

56.

Zhang Y, Wallace DL, de Lara CM, Ghattas H, Asquith B, Worth A, Griffin GE, Taylor GP, Tough DF, Beverley PC, Macallan DC (2007) In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunology 121(2):258–265. doi:10.1111/j.1365-2567.2007.02573.x CrossRefPubMedPubMedCentral

Titel: Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance
verfasst von: Angela R. Manser
Markus Uhrberg
Publikationsdatum: 19.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 4/2016
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-015-1750-0

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