Skip to main content

Advertisement

SpringerLink
Log in

CD57 in human natural killer cells and T-lymphocytes

  • Symposium-in-Writing Paper
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The CD57 antigen (alternatively HNK-1, LEU-7, or L2) is routinely used to identify terminally differentiated ‘senescent’ cells with reduced proliferative capacity and altered functional properties. In this article, we review current understanding of the attributes of CD57-expressing T-cells and NK cells in both health and disease and discuss how this marker can inform researchers about their likely functions in human blood and tissues in vivo. While CD57 expression on human lymphocytes indicates an inability to proliferate, these cells also display high cytotoxic potential, and CD57pos NK cells exhibit both memory-like features and potent effector functions. Accordingly, frequencies of CD57-expressing cells in blood and tissues have been correlated with clinical prognosis in chronic infections or various cancers and with human aging. Functional modulation of senescent CD57pos T-cells and mature CD57pos NK cells may therefore represent innovative strategies for protection against human immunological aging and/or various chronic diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CTLA-4:

Cytotoxic T-lymphocyte antigen 4

FLU:

Influenza virus

HBV:

Hepatitis B virus

HCMV:

Human cytomegalovirus

HCV:

Hepatitis C virus

HESN:

Highly HIV-exposed seronegative subjects

HIV:

Human immunodeficiency virus

KLRG1:

Killer cell lectin-like receptor G1

LAG-3:

Lymphocyte activation gene 3

PD-1:

Programmed cell death 1

SLAS:

Singapore Longitudinal Aging Studies

SPF:

Specific pathogen-free

TIM-3:

T-cell immunoglobulin domain and mucin domain protein 3

References

  1. Abo T, Balch CM (1981) A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127(3):1024–1029

    CAS  PubMed  Google Scholar 

  2. Yamamoto S, Oka S, Inoue M, Shimuta M, Manabe T, Takahashi H, Miyamoto M, Asano M, Sakagami J, Sudo K, Iwakura Y, Ono K, Kawasaki T (2002) Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning. J Biol Chem 277(30):27227–27231

    Article  CAS  PubMed  Google Scholar 

  3. Focosi D, Bestagno M, Burrone O, Petrini M (2010) CD57+ T lymphocytes and functional immune deficiency. J Leukoc Biol 87(1):107–116

    Article  CAS  PubMed  Google Scholar 

  4. Brenchley JM, Karandikar NJ, Betts MR, Ambrozak DR, Hill BJ, Crotty LE, Casazza JP, Kuruppu J, Migueles SA, Connors M, Roederer M, Douek DC, Koup RA (2003) Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 101(7):2711–2720

    Article  CAS  PubMed  Google Scholar 

  5. Palmer BE, Blyveis N, Fontenot AP, Wilson CC (2005) Functional and phenotypic characterization of CD57+ CD4+ T cells and their association with HIV-1-induced T cell dysfunction. J Immunol 175(12):8415–8423

    Article  CAS  PubMed  Google Scholar 

  6. Bandres E, Merino J, Vazquez B, Inoges S, Moreno C, Subira ML, Sanchez-Ibarrola A (2000) The increase of IFN-gamma production through aging correlates with the expanded CD8(+high) CD28(−) CD57(+) subpopulation. Clin Immunol 96(3):230–235

    Article  CAS  PubMed  Google Scholar 

  7. Strioga M, Pasukoniene V, Characiejus D (2011) CD8+ CD28− and CD8+ CD57+ T cells and their role in health and disease. Immunology 134(1):17–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Le Priol Y, Puthier D, Lecureuil C, Combadiere C, Debre P, Nguyen C, Combadiere B (2006) High cytotoxic and specific migratory potencies of senescent CD8+ CD57+ cells in HIV-infected and uninfected individuals. J Immunol 177(8):5145–5154

    Article  PubMed  Google Scholar 

  9. Petrovas C, Chaon B, Ambrozak DR, Price DA, Melenhorst JJ, Hill BJ, Geldmacher C, Casazza JP, Chattopadhyay PK, Roederer M, Douek DC, Mueller YM, Jacobson JM, Kulkarni V, Felber BK, Pavlakis GN, Katsikis PD, Koup RA (2009) Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection. J Immunol 183(2):1120–1132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Akbar AN, Henson SM (2011) Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat Rev Immunol 11(4):289–295

    Article  CAS  PubMed  Google Scholar 

  11. Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ (2009) Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 10(1):29–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R (2003) Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 77(8):4911–4927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chattopadhyay PK, Betts MR, Price DA, Gostick E, Horton H, Roederer M, De Rosa SC (2009) The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression. J Leukoc Biol 85(1):88–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chiang SC, Theorell J, Entesarian M, Meeths M, Mastafa M, Al-Herz W, Frisk P, Gilmour KC, Ifversen M, Langenskiold C, Machaczka M, Naqvi A, Payne J, Perez-Martinez A, Sabel M, Unal E, Unal S, Winiarski J, Nordenskjold M, Ljunggren HG, Henter JI, Bryceson YT (2013) Comparison of primary human cytotoxic T-cell and natural killer cell responses reveal similar molecular requirements for lytic granule exocytosis but differences in cytokine production. Blood 121(8):1345–1356

    Article  CAS  PubMed  Google Scholar 

  15. Sadat-Sowti B, Parrot A, Quint L, Mayaud C, Debre P, Autran B (1994) Alveolar CD8+ CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions. Am J Respir Crit Care Med 149(4 Pt 1):972–980

    Article  CAS  PubMed  Google Scholar 

  16. De Rosa SC, Mitra DK, Watanabe N, Herzenberg LA, Herzenberg LA, Roederer M (2001) Vdelta1 and Vdelta2 gammadelta T cells express distinct surface markers and might be developmentally distinct lineages. J Leukoc Biol 70(4):518–526

    PubMed  Google Scholar 

  17. Vasudev A, Ying CT, Ayyadhury S, Puan KJ, Andiappan AK, Nyunt MS, Shadan NB, Mustafa S, Low I, Rotzschke O, Fulop T, Ng TP, Larbi A (2014) gamma/delta T cell subsets in human aging using the classical alpha/beta T cell model. J Leukoc Biol 96(4):647–655

    Article  PubMed  Google Scholar 

  18. Henson SM, Lanna A, Riddell NE, Franzese O, Macaulay R, Griffiths SJ, Puleston DJ, Watson AS, Simon AK, Tooze SA, Akbar AN (2014) p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8(+) T cells. J Clin Invest 124(9):4004–4016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ouyang Q, Wagner WM, Voehringer D, Wikby A, Klatt T, Walter S, Muller CA, Pircher H, Pawelec G (2003) Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1). Exp Gerontol 38(8):911–920

    Article  CAS  PubMed  Google Scholar 

  20. Voehringer D, Koschella M, Pircher H (2002) Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood 100(10):3698–3702

    Article  CAS  PubMed  Google Scholar 

  21. Ibegbu CC, Xu YX, Harris W, Maggio D, Miller JD, Kourtis AP (2005) Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57. J Immunol 174(10):6088–6094

    Article  CAS  PubMed  Google Scholar 

  22. McMahon CW, Zajac AJ, Jamieson AM, Corral L, Hammer GE, Ahmed R, Raulet DH (2002) Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells. J Immunol 169(3):1444–1452

    Article  CAS  PubMed  Google Scholar 

  23. Voehringer D, Blaser C, Brawand P, Raulet DH, Hanke T, Pircher H (2001) Viral infections induce abundant numbers of senescent CD8 T cells. J Immunol 167(9):4838–4843

    Article  CAS  PubMed  Google Scholar 

  24. Vallejo AN (2005) CD28 extinction in human T cells: altered functions and the program of T-cell senescence. Immunol Rev 205:158–169

    Article  CAS  PubMed  Google Scholar 

  25. Ortiz-Suarez A, Miller RA (2002) A subset of CD8 memory T cells from old mice have high levels of CD28 and produce IFN-gamma. Clin Immunol 104(3):282–292

    Article  CAS  PubMed  Google Scholar 

  26. Kared H, Camous X, Larbi A (2014) T cells and their cytokines in persistent stimulation of the immune system. Curr Opin Immunol 29:79–85

    Article  CAS  PubMed  Google Scholar 

  27. Papagno L, Spina CA, Marchant A, Salio M, Rufer N, Little S, Dong T, Chesney G, Waters A, Easterbrook P, Dunbar PR, Shepherd D, Cerundolo V, Emery V, Griffiths P, Conlon C, McMichael AJ, Richman DD, Rowland-Jones SL, Appay V (2004) Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol 2(2):E20

    Article  PubMed  PubMed Central  Google Scholar 

  28. Scheinberg P, Melenhorst JJ, Brenchley JM, Hill BJ, Hensel NF, Chattopadhyay PK, Roederer M, Picker LJ, Price DA, Barrett AJ, Douek DC (2009) The transfer of adaptive immunity to CMV during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor. Blood 114(24):5071–5080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Maurer T, Ponte M, Leslie K (2007) HIV-associated Kaposi’s sarcoma with a high CD4 count and a low viral load. N Engl J Med 357(13):1352–1353

    Article  CAS  PubMed  Google Scholar 

  30. Weekes MP, Wills MR, Mynard K, Hicks R, Sissons JGP, Carmichael AJ (1999) Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57(+) CD28(−) CD8(+) T-cell population. Immunology 98(3):443–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Lofgren S, Nilsson BO, Ernerudh J, Pawelec G, Johansson B (2005) An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J Gerontol A Biol Sci Med Sci 60(5):556–565

    Article  PubMed  Google Scholar 

  32. Franceschi C, Bonafe M, Valensin S (2000) Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine 18(16):1717–1720

    Article  CAS  PubMed  Google Scholar 

  33. Wertheimer AM, Bennett MS, Park B, Uhrlaub JL, Martinez C, Pulko V, Currier NL, Nikolich-Zugich D, Kaye J, Nikolich-Zugich J (2014) Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans. J Immunol 192(5):2143–2155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dolfi DV, Mansfield KD, Polley AM, Doyle SA, Freeman GJ, Pircher H, Schmader KE, Wherry EJ (2013) Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans. J Leukoc Biol 93(6):825–836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Characiejus D, Pasukoniene V, Kazlauskaite N, Valuckas KP, Petraitis T, Mauricas M, Den Otter W (2002) Predictive value of CD8highCD57+ lymphocyte subset in interferon therapy of patients with renal cell carcinoma. Anticancer Res 22(6B):3679–3683

    PubMed  Google Scholar 

  36. Characiejus D, Ukoniene VP, Auskaite RJ, Azlauskaite N, Aleknavicius E, Mauricas M, Den Otter W (2008) Peripheral blood CD8highCD57+ lymphocyte levels may predict outcome in melanoma patients treated with adjuvant interferon-alpha. Anticancer Res 28(2B):1139–1142

    CAS  PubMed  Google Scholar 

  37. Akagi J, Baba H (2008) Prognostic value of CD57(+) T lymphocytes in the peripheral blood of patients with advanced gastric cancer. Int J Clin Oncol 13(6):528–535

    Article  CAS  PubMed  Google Scholar 

  38. Characiejus D, Pasukoniene V, Jacobs JJ, Eidukevicius R, Jankevicius F, Dobrovolskiene N, Mauricas M, Van Moorselaar RJ, Den Otter W (2011) Prognostic significance of peripheral blood CD8highCD57+ lymphocytes in bladder carcinoma patients after intravesical IL-2. Anticancer Res 31(2):699–703

    CAS  PubMed  Google Scholar 

  39. Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, Villaggio B, Ferrera A, Kunkl A, Rizzi M, Ferrera F, Balestra P, Ghio M, Contini P, Setti M, Olive D, Azzarone B, Carmignani G, Ravetti JL, Torre G, Indiveri F (2007) CD8+ CD28− T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol 179(7):4323–4334

    Article  CAS  PubMed  Google Scholar 

  40. Gutkin DW, Shurin MR (2014) Clinical evaluation of systemic and local immune responses in cancer: time for integration. Cancer Immunol Immunother 63(1):45–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tsukishiro T, Donnenberg AD, Whiteside TL (2003) Rapid turnover of the CD8(+) CD28(−) T-cell subset of effector cells in the circulation of patients with head and neck cancer. Cancer Immunol Immunother 52(10):599–607

    Article  PubMed  Google Scholar 

  42. Van den Hove LE, Vandenberghe P, Van Gool SW, Ceuppens JL, Demuynck H, Verhoef GE, Boogaerts MA (1998) Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment. Leuk Res 22(2):175–184

    Article  PubMed  Google Scholar 

  43. Atayar C, Poppema S, Visser L, van den Berg A (2006) Cytokine gene expression profile distinguishes CD4+/CD57+ T cells of the nodular lymphocyte predominance type of Hodgkin’s lymphoma from their tonsillar counterparts. J Pathol 208(3):423–430

    Article  CAS  PubMed  Google Scholar 

  44. Serrano D, Monteiro J, Allen SL, Kolitz J, Schulman P, Lichtman SM, Buchbinder A, Vinciguerra VP, Chiorazzi N, Gregersen PK (1997) Clonal expansion within the CD4+ CD57+ and CD8+ CD57+ T cell subsets in chronic lymphocytic leukemia. J Immunol 158(3):1482–1489

    CAS  PubMed  Google Scholar 

  45. Sze DM, Brown RD, Yuen E, Gibson J, Ho J, Raitakari M, Basten A, Joshua DE, de St Fazekas, Groth B (2003) Clonal cytotoxic T cells in myeloma. Leuk Lymphoma 44(10):1667–1674

    Article  CAS  PubMed  Google Scholar 

  46. Mileshkin L, Honemann D, Gambell P, Trivett M, Hayakawa Y, Smyth M, Beshay V, Ritchie D, Simmons P, Milner AD, Zeldis JB, Prince HM (2007) Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome. Haematologica 92(8):1075–1082

    Article  CAS  PubMed  Google Scholar 

  47. Nunes C, Wong R, Mason M, Fegan C, Man S, Pepper C (2012) Expansion of a CD8(+) PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clin Cancer Res 18(3):678–687

    Article  CAS  PubMed  Google Scholar 

  48. Dobrovolskiene NT, Cicenas S, Kazlauskaite N, Miseikyte-Kaubriene E, Krasko JA, Ostapenko V, Pasukoniene V, Strioga MM (2015) CD8CD57 T-cell population as an independent predictor of response to chemoradiation therapy in extensive-stage small cell lung cancer. Lung Cancer 90(2):326–333

    Article  PubMed  Google Scholar 

  49. Bottomley M, Harden P, Wood K (2015) CD57 expression in CD8 T cells and development of cutaneous squamous cell carcinoma in renal transplant recipients: a prospective cohort study. Lancet 385(Suppl 1):S23

    Article  PubMed  Google Scholar 

  50. Lin YX, Yan LN, Li B, Wang LL, Wen TF, Zeng Y, Wang WT, Zhao JC, Yang JY, Xu MQ, Ma YK, Chen ZY, Bai YJ (2009) A significant expansion of CD8+ CD28− T-suppressor cells in adult-to-adult living donor liver transplant recipients. Transplant Proc 41(10):4229–4231

    Article  CAS  PubMed  Google Scholar 

  51. Vlad G, Cortesini R, Suciu-Foca N (2008) CD8+ T suppressor cells and the ILT3 master switch. Hum Immunol 69(11):681–686

    Article  CAS  PubMed  Google Scholar 

  52. Sabnani I, Zucker MJ, Tsang P, Palekar S (2006) Clonal T-large granular lymphocyte proliferation in solid organ transplant recipients. Transplant Proc 38(10):3437–3440

    Article  CAS  PubMed  Google Scholar 

  53. Nielsen CM, White MJ, Goodier MR, Riley EM (2013) Functional Significance of CD57 Expression on human NK Cells and relevance to disease. Front Immunol 4:422

    Article  PubMed  PubMed Central  Google Scholar 

  54. Mikulkova Z, Praksova P, Stourac P, Bednarik J, Strajtova L, Pacasova R, Belobradkova J, Dite P, Michalek J (2010) Numerical defects in CD8+ CD28− T-suppressor lymphocyte population in patients with type 1 diabetes mellitus and multiple sclerosis. Cell Immunol 262(2):75–79

    Article  CAS  PubMed  Google Scholar 

  55. Tulunay A, Yavuz S, Direskeneli H, Eksioglu-Demiralp E (2008) CD8+ CD28−, suppressive T cells in systemic lupus erythematosus. Lupus 17(7):630–637

    Article  CAS  PubMed  Google Scholar 

  56. 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 CD56dimCD16+ NK-cell subset. Blood 116(19):3865–3874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. 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 CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood 116(19):3853–3864

    Article  PubMed  Google Scholar 

  58. Brunetta E, Hudspeth KL, Mavilio D (2010) Pathologic natural killer cell subset redistribution in HIV-1 infection: new insights in pathophysiology and clinical outcomes. J Leukoc Biol 88(6):1119–1130

    Article  CAS  PubMed  Google Scholar 

  59. Carrega P, Ferlazzo G (2012) Natural killer cell distribution and trafficking in human tissues. Front Immunol 3:347

    Article  PubMed  PubMed Central  Google Scholar 

  60. Strauss-Albee DM, Horowitz A, Parham P, Blish CA (2014) Coordinated regulation of NK receptor expression in the maturing human immune system. J Immunol 193(10):4871–4879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lugli E, Marcenaro E, Mavilio D (2014) NK Cell Subset Redistribution during the Course of Viral Infections. Front Immunol 5:390

    Article  PubMed  PubMed Central  Google Scholar 

  62. Mela CM, Goodier MR (2007) The contribution of cytomegalovirus to changes in NK cell receptor expression in HIV-1-infected individuals. J Infect Dis 195(1):158–159; author reply 159-160

  63. 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

    Article  PubMed  Google Scholar 

  64. Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457(7229):557–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Prod’homme V, Griffin C, Aicheler RJ, Wang EC, McSharry BP, Rickards CR, Stanton RJ, Borysiewicz LK, Lopez-Botet M, Wilkinson GW, Tomasec P (2007) The human cytomegalovirus MHC class I homolog UL18 inhibits LIR-1+ but activates LIR-1− NK cells. J Immunol 178(7):4473–4481

    Article  PubMed  PubMed Central  Google Scholar 

  66. Goodier MR, White MJ, Darboe A, Nielsen CM, Goncalves A, Bottomley C, Moore SE, Riley EM (2014) Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions. Blood 124(14):2213–2222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hendricks DW, Balfour HH Jr, Dunmire SK, Schmeling DO, Hogquist KA, Lanier LL (2014) Cutting edge: NKG2C(hi)CD57+ NK cells respond specifically to acute infection with cytomegalovirus and not Epstein–Barr virus. J Immunol 192(10):4492–4496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. White MJ, Nielsen CM, McGregor RH, Riley EH, Goodier MR (2014) Differential activation of CD57-defined natural killer cell subsets during recall responses to vaccine antigens. Immunology 142(1):140–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ahmad F, Hong HS, Jackel M, Jablonka A, Lu IN, Bhatnagar N, Eberhard JM, Bollmann BA, Ballmaier M, Zielinska-Skowronek M, Schmidt RE, Meyer-Olson D (2014) High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression. J Virol 88(21):12397–12408

    Article  PubMed  PubMed Central  Google Scholar 

  70. Brunetta E, Fogli M, Varchetta S, Bozzo L, Hudspeth KL, Marcenaro E, Moretta A, Mavilio D (2009) The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia. Blood 114(18):3822–3830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhao JJ, Pan QZ, Pan K, Weng DS, Wang QJ, Li JJ, Lv L, Wang DD, Zheng HX, Jiang SS, Zhang XF, Xia JC (2014) Interleukin-37 mediates the antitumor activity in hepatocellular carcinoma: role for CD57+ NK cells. Sci Rep 4:5177

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Lopez-Verges S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, Houchins JP, Miller S, Kang SM, Norris PJ, Nixon DF, Lanier LL (2011) Expansion of a unique CD57(+)NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci USA 108(36):14725–14732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bhatnagar N, Ahmad F, Hong HS, Eberhard J, Lu IN, Ballmaier M, Schmidt RE, Jacobs R, Meyer-Olson D (2014) FcgammaRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcgammaRII (CD32). Eur J Immunol 44(11):3368–3379

    Article  CAS  PubMed  Google Scholar 

  74. Holmes TD, Wilson EB, Black EV, Benest AV, Vaz C, Tan B, Tanavde VM, Cook GP (2014) Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT. Proc Natl Acad Sci USA 111(52):E5688–E5696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 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

    Article  PubMed  Google Scholar 

  76. Borysiewicz LK, Rodgers B, Morris S, Graham S, Sissons JG (1985) Lysis of human cytomegalovirus infected fibroblasts by natural killer cells: demonstration of an interferon-independent component requiring expression of early viral proteins and characterization of effector cells. J Immunol 134(4):2695–2701

    CAS  PubMed  Google Scholar 

  77. Lima JF, Oliveira LM, Pereira NZ, Mitsunari GE, Duarte AJ, Sato MN (2014) Distinct natural killer cells in HIV-exposed seronegative subjects with effector cytotoxic CD56(dim) and CD56(bright) cells and memory-like CD57(+) NKG2C(+) CD56(dim) cells. J Acquir Immune Defic Syndr 67(5):463–471

    Article  CAS  PubMed  Google Scholar 

  78. Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L (2012) Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 12(4):239–252

    Article  CAS  PubMed  Google Scholar 

  79. Balch CM, Tilden AB, Dougherty PA, Cloud GA (1983) Depressed levels of granular lymphocytes with natural killer (NK) cell function in 247 cancer patients. Ann Surg 198(2):192–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ali TH, Pisanti S, Ciaglia E, Mortarini R, Anichini A, Garofalo C, Tallerico R, Santinami M, Gulletta E, Ietto C, Galgani M, Matarese G, Bifulco M, Ferrone S, Colucci F, Moretta A, Karre K, Carbone E (2014) Enrichment of CD56(dim)KIR+ CD57+ highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients. Nat Commun 5:5639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Matsumura G (1990) Leu7 (HNK-1)-positive cells in peripheral blood and natural killer cell activity in patients with atopic dermatitis. Nihon Hifuka Gakkai Zasshi 100(1):57–62

    CAS  PubMed  Google Scholar 

  82. Batista MD, Ho EL, Kuebler PJ, Milush JM, Lanier LL, Kallas EG, York VA, Chang D, Liao W, Unemori P, Leslie KS, Maurer T, Nixon DF (2013) Skewed distribution of natural killer cells in psoriasis skin lesions. Exp Dermatol 22(1):64–66

    Article  PubMed  PubMed Central  Google Scholar 

  83. Ottaviani C, Nasorri F, Bedini C, de Pita O, Girolomoni G, Cavani A (2006) CD56brightCD16(−) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation. Eur J Immunol 36(1):118–128

    Article  CAS  PubMed  Google Scholar 

  84. Dalbeth N, Callan MF (2002) A subset of natural killer cells is greatly expanded within inflamed joints. Arthritis Rheum 46(7):1763–1772

    Article  PubMed  Google Scholar 

  85. Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, Mosca F, Boggi U, Muda AO, Del Prato S, Elliott JF, Covacci A, Rappuoli R, Roep BO, Marchetti P (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci USA 104(12):5115–5120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. van Helden MJ, Goossens S, Daussy C, Mathieu AL, Faure F, Marcais A, Vandamme N, Farla N, Mayol K, Viel S, Degouve S, Debien E, Seuntjens E, Conidi A, Chaix J, Mangeot P, de Bernard S, Buffat L, Haigh JJ, Huylebroeck D, Lambrecht BN, Berx G, Walzer T (2015) Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection. J Exp Med 212(12):2015–2025. doi:10.1084/jem.20150809

    Article  PubMed  Google Scholar 

  87. Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, Seuntjens E, Stryjewska A, Zweier C, Roychoudhuri R, Gattinoni L, Bird LM, Higashi Y, Kondoh H, Huylebroeck D, Haigh J, Goldrath AW (2015) Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J Exp Med 212(12):2027–2039. doi:10.1084/jem.20150194

    Article  PubMed  Google Scholar 

  88. Lee SA, Sinclair E, Jain V, Huang Y, Epling L, Van Natta M, Meinert CL, Martin JN, McCune JM, Deeks SG, Lederman MM, Hecht FM, Hunt PW (2014) Low proportions of CD28− CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection. J Infect Dis 210(3):374–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Serrano-Villar S, Sainz T, Lee SA, Hunt PW, Sinclair E, Shacklett BL, Ferre AL, Hayes TL, Somsouk M, Hsue PY, Van Natta ML, Meinert CL, Lederman MM, Hatano H, Jain V, Huang Y, Hecht FM, Martin JN, McCune JM, Moreno S, Deeks SG (2014) HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality. PLoS Pathog 10(5):e1004078

    Article  PubMed  PubMed Central  Google Scholar 

  90. Di Mitri D, Azevedo RI, Henson SM, Libri V, Riddell NE, Macaulay R, Kipling D, Soares MV, Battistini L, Akbar AN (2011) Reversible senescence in human CD4+ CD45RA+ CD27− memory T cells. J Immunol 187(5):2093–2100

    Article  PubMed  Google Scholar 

  91. Henson SM, Macaulay R, Riddell NE, Nunn CJ, Akbar AN (2015) Blockade of PD-1 or p38 MAP kinase signaling enhances senescent human CD8(+) T-cell proliferation by distinct pathways. Eur J Immunol 45(5):1441–1451

    Article  CAS  PubMed  Google Scholar 

  92. Libri V, Azevedo RI, Jackson SE, Di Mitri D, Lachmann R, Fuhrmann S, Vukmanovic-Stejic M, Yong K, Battistini L, Kern F, Soares MV, Akbar AN (2011) Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+ CD45RA+ CD27+ T cells: the potential involvement of interleukin-7 in this process. Immunology 132(3):326–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lanna A, Coutavas E, Levati L, Seidel J, Rustin MH, Henson SM, Akbar AN, Franzese O (2013) IFN-alpha inhibits telomerase in human CD8(+) T cells by both hTERT downregulation and induction of p38 MAPK signaling. J Immunol 191(7):3744–3752

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by a research grant from the Agency for Science, Technology and Research (SIgN collaborative Grant No. 10–036) and by the Singapore Immunology Network. Anis Larbi is a scholar of the International Society for Advancement of Cytometry (ISAC). Serena Martelli is funded by the A*STAR Research Attachment Program (ARAP) and the Vice Chancellor Scholarship, University of Southampton.

Author information

Authors and Affiliations

  1. Singapore Immunology Network (SIgN), Aging and Immunity Program, Agency for Science Technology and Research (A*STAR), 8A Biomedical Grove #3 Immunos, Singapore, 138648, Republic of Singapore

    Hassen Kared, Serena Martelli & Anis Larbi

  2. Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK

    Serena Martelli & Sylvia L.F. Pender

  3. Gerontological Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore

    Tze Pin Ng

  4. Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore

    Anis Larbi

  5. School of Biological Sciences, Nanyang Technological University, Singapore, Republic of Singapore

    Anis Larbi

Authors
  1. Hassen Kared
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serena Martelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tze Pin Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sylvia L.F. Pender
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anis Larbi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hassen Kared.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

This article is part of the Symposium-in-Writing “Natural killer cells, ageing and cancer”, a series of papers published in Cancer Immunology, Immunotherapy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kared, H., Martelli, S., Ng, T.P. et al. CD57 in human natural killer cells and T-lymphocytes. Cancer Immunol Immunother 65, 441–452 (2016). https://doi.org/10.1007/s00262-016-1803-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-016-1803-z

Keywords

Search

Navigation