open access

Vol 56, No 4 (2018)
Original paper
Submitted: 2018-12-19
Accepted: 2018-12-19
Published online: 2019-01-02
Get Citation

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

Lucyna Kaszubowska1, Jerzy Foerster2, Przemysław Kwiatkowski3, Daria Schetz4
·
Pubmed: 30633320
·
Folia Histochem Cytobiol 2018;56(4):231-240.
Affiliations
  1. Department of Histology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland
  2. Department of Social and Clinical Gerontology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland
  3. Department of Human Histology and Embryology, Collegium Medicum, Faculty of Medicine, University of Warmia and Masuria in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland
  4. Department of Pharmacology, Medical University of Gdańsk, Dębowa 23, 80-204 Gdańsk, Poland

open access

Vol 56, No 4 (2018)
ORIGINAL PAPERS
Submitted: 2018-12-19
Accepted: 2018-12-19
Published online: 2019-01-02

Abstract

Introduction. NKT-like cells are “non-classical”, “CD1d-independent” NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing.
Material and methods. The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess the NKT-like (CD3+CD56+) and T (CD3+) cell populations.
Results. The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable.
Conclusions. The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.

Abstract

Introduction. NKT-like cells are “non-classical”, “CD1d-independent” NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing.
Material and methods. The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess the NKT-like (CD3+CD56+) and T (CD3+) cell populations.
Results. The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable.
Conclusions. The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.

Get Citation

Keywords

lymphocytes; CD3+ cells; NKT-like cells; CD3+CD56+ cells; ageing; immunosenescence; seniors; SIRT1; HSP70; SOD2

About this article
Title

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 56, No 4 (2018)

Article type

Original paper

Pages

231-240

Published online

2019-01-02

Page views

2538

Article views/downloads

1618

DOI

10.5603/FHC.a2018.0025

Pubmed

30633320

Bibliographic record

Folia Histochem Cytobiol 2018;56(4):231-240.

Keywords

lymphocytes
CD3+ cells
NKT-like cells
CD3+CD56+ cells
ageing
immunosenescence
seniors
SIRT1
HSP70
SOD2

Authors

Lucyna Kaszubowska
Jerzy Foerster
Przemysław Kwiatkowski
Daria Schetz

References (51)
  1. Tarazona R, DelaRosa O, Alonso C, et al. Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells. Mechanisms of Ageing and Development. 2001; 121(1-3): 77–88.
  2. Pita-López ML, Pera A, Solana R. Adaptive Memory of Human NK-like CD8 T-Cells to Aging, and Viral and Tumor Antigens. Front Immunol. 2016; 7: 616.
  3. Torina A, Guggino G, La Manna MP, et al. The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases. Int J Mol Sci. 2018; 19(2).
  4. Peralbo E, Alonso C, Solana R. Invariant NKT and NKT-like lymphocytes: two different T cell subsets that are differentially affected by ageing. Exp Gerontol. 2007; 42(8): 703–708.
  5. Panda A, Arjona A, Sapey E, et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 2009; 30(7): 325–333.
  6. Solana R, Mariani E. NK and NK/T cells in human senescence. Vaccine. 2000; 18(16): 1613–1620.
  7. Lemster BH, Michel JJ, Montag DT, et al. Induction of CD56 and TCR-Independent Activation of T Cells with Aging. The Journal of Immunology. 2008; 180(3): 1979–1990.
  8. Godfrey DI, MacDonald HR, Kronenberg M, et al. NKT cells: what's in a name? Nat Rev Immunol. 2004; 4(3): 231–237.
  9. Jiang Y, Cui X, Cui C, et al. The function of CD3+CD56+ NKT-like cells in HIV-infected individuals. Biomed Res Int. 2014; 2014: 863625.
  10. Kelly-Rogers J, Madrigal-Estebas L, O'Connor T, et al. Activation-induced expression of CD56 by T cells is associated with a reprogramming of cytolytic activity and cytokine secretion profile in vitro. Hum Immunol. 2006; 67(11): 863–873.
  11. Dunne J, Lynch S, O'Farrelly C, et al. Selective Expansion and Partial Activation of Human NK Cells and NK Receptor-Positive T Cells by IL-2 and IL-15. The Journal of Immunology. 2001; 167(6): 3129–3138.
  12. Chen YJ, Liao HF. NK/NKT Cells and Aging. International Journal of Gerontology. 2007; 1(2): 65–76.
  13. FRANCESCHI C, BONAFÈ M, VALENSIN S, et al. Inflamm-aging: An Evolutionary Perspective on Immunosenescence. Annals of the New York Academy of Sciences. 2006; 908(1): 244–254.
  14. Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing [Internet]. 2005/05/21. 2005;2:8. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15904534.
  15. Müller L, Pawelec G. As we age: Does slippage of quality control in the immune system lead to collateral damage? Ageing Res Rev. 2015; 23(Pt A): 116–123.
  16. Frasca D, Blomberg BB. Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology. 2016; 17(1): 7–19.
  17. Bektas A, Schurman SH, Sen R, et al. Aging, inflammation and the environment. Exp Gerontol. 2018; 105: 10–18.
  18. Höhn A, Weber D, Jung T, et al. Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence. Redox Biol. 2017; 11: 482–501.
  19. Kaszubowska L, Kaczor JJ, Hak L, et al. Sensitivity of natural killer cells to activation in the process of ageing is related to the oxidative and inflammatory status of the elderly. J Physiol Pharmacol. 2011; 62(1): 101–109.
  20. Kaszubowska L, Foerster J, Kaczor JJ, et al. Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors. Immun Ageing. 2017; 14: 3.
  21. Kaszubowska L, Foerster J, Kaczor JJ, et al. NK cells of the oldest seniors represent constant and resistant to stimulation high expression of cellular protective proteins SIRT1 and HSP70. Immun Ageing. 2018; 15: 12.
  22. Afolayan AJ, Teng RJ, Eis A, et al. Inducible HSP70 regulates superoxide dismutase-2 and mitochondrial oxidative stress in the endothelial cells from developing lungs. Am J Physiol Lung Cell Mol Physiol. 2014; 306(4): L351–L360.
  23. Zemanovic S, Ivanov MV, Ivanova LV, et al. Dynamic Phosphorylation of the C Terminus of Hsp70 Regulates the Mitochondrial Import of SOD2 and Redox Balance. Cell Rep. 2018; 25(9): 2605–2616.e7.
  24. Martínez de Toda I, De la Fuente M. The role of Hsp70 in oxi-inflamm-aging and its use as a potential biomarker of lifespan. Biogerontology. 2015; 16(6): 709–721.
  25. Santos L, Escande C, Denicola A. Potential Modulation of Sirtuins by Oxidative Stress. Oxid Med Cell Longev. 2016; 2016: 9831825.
  26. Langley E. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. The EMBO Journal. 2002; 21(10): 2383–2396.
  27. Vaziri H, Dessain S, Eaton E, et al. hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase. Cell. 2001; 107(2): 149–159.
  28. Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004; 303(5666): 2011–2015.
  29. Motta M, Divecha N, Lemieux M, et al. Mammalian SIRT1 Represses Forkhead Transcription Factors. Cell. 2004; 116(4): 551–563.
  30. Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004; 23(12): 2369–2380.
  31. Longo VD. Linking sirtuins, IGF-I signaling, and starvation. Exp Gerontol. 2009; 44(1-2): 70–74.
  32. van der Horst A, Tertoolen LGJ, de Vries-Smits LMM, et al. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem. 2004; 279(28): 28873–28879.
  33. Merksamer PI, Liu Y, He W, et al. The sirtuins, oxidative stress and aging: an emerging link. Aging (Albany NY). 2013; 5(3): 144–150.
  34. Njemini R, Bautmans I, Lambert M, et al. Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation. Mech Ageing Dev. 2007; 128(7-8): 450–454.
  35. Njemini R, Demanet C, Mets T. Aging-related differences in basal heat shock protein 70 levels in lymphocytes are linked to altered frequencies of lymphocyte subsets. Aging Cell. 2008; 7(4): 498–505.
  36. Li Y, Ohms SJ, Sun C, et al. NF-κB controls Il2 and Csf2 expression during T cell development and activation process. Mol Biol Rep. 2013; 40(2): 1685–1692.
  37. Folstein M, Folstein S, McHugh P. “Mini-mental state”. Journal of Psychiatric Research. 1975; 12(3): 189–198.
  38. Katz S. Studies of Illness in the Aged. JAMA. 1963; 185(12): 914.
  39. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes & Development. 1999; 13(19): 2570–2580.
  40. Lin SJ. Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae. Science. 2000; 289(5487): 2126–2128.
  41. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001; 410(6825): 227–230.
  42. Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004; 101(45): 15998–16003.
  43. Westerheide SD, Anckar J, Stevens SM, et al. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science. 2009; 323(5917): 1063–1066.
  44. Beier UH, Akimova T, Liu Y, et al. Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells. Curr Opin Immunol. 2011; 23(5): 670–678.
  45. West JD, Wang Y, Morano KA. Small molecule activators of the heat shock response: chemical properties, molecular targets, and therapeutic promise. Chem Res Toxicol. 2012; 25(10): 2036–2053.
  46. Paul A, Belton A, Nag S, et al. Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging. Mech Ageing Dev. 2007; 128(11-12): 706–716.
  47. Rodriguez-Iturbe B, Sepassi L, Quiroz Y, et al. Association of mitochondrial SOD deficiency with salt-sensitive hypertension and accelerated renal senescence. J Appl Physiol (1985). 2007; 102(1): 255–260.
  48. Miyaji C, Watanabe H, Minagawa M, Toma H, Kawamura T, Nohara Y, et al. Numerical and functional characteristics of lymphocyte subsets in centenarians. J. Clin. Immunol. [Internet]. 1997 [cited 2018 Dec 14];17:420–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9327342.
  49. Wei Li, Zhao J, Wu W, et al. Decreased absolute numbers of CD3 T cells and CD8 T cells during aging in herpes zoster patients. Sci Rep. 2017; 7(1): 15039.
  50. Tavares SM, Junior Wd, Lopes E Silva MR. Normal lymphocyte immunophenotype in an elderly population. Rev Bras Hematol Hemoter. 2014; 36(3): 180–183.
  51. Kaszubowska L, Foerster J, Schetz D, et al. CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2. Immun Ageing. 2018; 15: 31.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl