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Aged T cells and cardiovascular disease

Cellular & Molecular Immunology volume 14, pages 1009–1010 (2017)Cite this article

Memory T cells undergo replicative senescence via repetitive proliferation. As in other cells, replicative senescence of T cells is characterized by shortened telomeres.1 Immunophenotypes are also altered in replicative senescent T cells compared to young T cells. In humans, replicative senescent T cells typically lose expression of CD28, a co-stimulatory receptor, and acquire the expression of CD57 antigen, a terminally sulfated glycan carbohydrateepitope,1 though the mechanism underlying this regulation has not yet been clearly elucidated. Therefore, CD28− or CD57+ T cells are considered replicative senescent T cells in humans, and the frequency of CD28− or CD57+ T cells in the peripheral blood increases with aging.2, 3

In principle, replicative senescence of T cells can be induced by any antigen or microbial pathogen if it is encountered repetitively. Among various human pathogens, cytomegalovirus (CMV) is the major virus responsible for the accumulation of replicative senescent CD28− or CD57+ T cells in humans.10, 11 CMV is a human herpesvirus that latently infects a majority of the population. CMV usually infects individuals asymptomatically during early childhood and establishes a lifelong latent infection,10, 11 but it is occasionally reactivated even in non-immunocompromised healthy hosts depending on the immune status of the host over their lifetime. Repetitive cycles of CMV reactivation and resolution result in repetitive antigenic stimulation of CMV-specific memory T cells and consequent accumulation of replicative senescent CMV-specific T cells over a person’s lifetime.10, 11, 12 A sustained increase and maintenance of CMV-specific memory T cells over a lifetime is known as ‘memory inflation’.10, 12

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References

  1. Akbar AN, Henson SM, Lanna A . Senescence of T lymphocytes: implications for enhancing human immunity. Trends Immunol 2016; 37: 866–876.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Weng NP, Akbar AN, Goronzy J . CD28(−) T cells: their role in the age-associated decline of immune function. Trends Immunol 2009; 30: 306–312.

    Article  CAS  Google Scholar 

  4. Pereira BI, Akbar AN . Convergence of innate and adaptive immunity during human aging. Front Immunol 2016; 7: 445.

    PubMed  PubMed Central  Google Scholar 

  5. Yu HT, Park S, Shin EC, Lee WW . T cell senescence and cardiovascular diseases. Clin Exp Med 2016; 16: 257–263.

    Article  CAS  Google Scholar 

  6. Henson SM, Lanna A, Riddell NE, Franzese O, Macaulay R, Griffiths SJ et al. p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8(+) T cells. J Clin Invest 2014; 124: 4004–4016.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Lanna A, Henson SM, Escors D, Akbar AN . The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat Immunol 2014; 15: 965–972.

    Article  CAS  Google Scholar 

  9. Lanna A, Gomes DC, Muller-Durovic B, McDonnell T, Escors D, Gilroy DW et al. A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging. Nat Immunol 2017; 18: 354–363.

    Article  CAS  Google Scholar 

  10. Kim J, Kim AR, Shin EC . Cytomegalovirus infection and memory T cell inflation. Immune Netw 2015; 15: 186–190.

    Article  Google Scholar 

  11. Nikolich-Zugich J . Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol 2008; 8: 512–522.

    Article  CAS  Google Scholar 

  12. Klenerman P, Oxenius A . T cell responses to cytomegalovirus. Nat Rev Immunol 2016; 16: 367–377.

    Article  CAS  Google Scholar 

  13. Liuzzo G, Kopecky SL, Frye RL, O'Fallon WM, Maseri A, Goronzy JJ et al. Perturbation of the T-cell repertoire in patients with unstable angina. Circulation 1999; 100: 2135–2139.

    Article  CAS  Google Scholar 

  14. Liuzzo G, Biasucci LM, Trotta G, Brugaletta S, Pinnelli M, Digianuario G et al. Unusual CD4+CD28null T lymphocytes and recurrence of acute coronary events. J Am Coll Cardiol 2007; 50: 1450–1458.

    Article  CAS  Google Scholar 

  15. Samani NJ, Boultby R, Butler R, Thompson JR, Goodall AH . Telomere shortening in atherosclerosis. Lancet 2001; 358: 472–473.

    Article  CAS  Google Scholar 

  16. Youn JC, Yu HT, Lim BJ, Koh MJ, Lee J, Chang DY et al. Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension 2013; 62: 126–133.

    Article  CAS  Google Scholar 

  17. Tae YuH, Youn JC, Lee J, Park S, Chi HS, Lee J et al. Characterization of CD8(+)CD57(+) T cells in patients with acute myocardial infarction. Cell Mol Immunol 2015; 12: 466–473.

    Article  Google Scholar 

  18. Yu HT, Youn JC, Kim JH, Seong YJ, Park SH, Kim HC et al. Arterial stiffness is associated with cytomegalovirus-specific senescent CD8+ T cells. J Am Heart Assoc 2017; 6: e006535.

    PubMed  PubMed Central  Google Scholar 

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  1. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, 34141, Republic of Korea

    Min Kyung Jung & Eui-Cheol Shin

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Jung, M., Shin, EC. Aged T cells and cardiovascular disease. Cell Mol Immunol 14, 1009–1010 (2017). https://doi.org/10.1038/cmi.2017.111

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