CoChat
Sign Up
Cited by 180T-cell and B-cell ImmunologyTelomeres, Telomerase, and SenescenceHIV Research and Treatment

Properties of end-stage human T cells defined by CD45RA re-expression

Open access
Henson, Sian M, Riddell, Natalie E, Akbar, Arne N·2012·Current Opinion in Immunology
DOI 10.1016/j.coi.2012.04.001
Open this paper in CoChat — free accountOpen PDF

Abstract

Persistent viral infections, inflammatory syndromes and ageing all induce the accumulation of highly differentiated CD45RA re-expressing memory T cells. These cells increase during ageing, especially in individuals who are infected with cytomegalovirus (CMV). These cells have decreased proliferative capacity, increased activation of senescence signalling pathways and greater susceptibility to apoptosis in vitro. However these cells are capable of multiple effector functions and thus bear all the hallmarks of short-lived effector T cells. This indicates that senescence signalling may govern the unique characteristics of effector T cells. In this article, we address the functional and migratory properties of these T cells and mechanisms that are involved in their generation. Finally we assess the potential for manipulation of their activity and whether this may improve immune function during ageing.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.coi.2012.04.001

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The TEMRA population that increases with age, especially in CD8+ cells, is highly oligoclonal, with single clonotypes reaching up to 1% of peripheral blood.

    “The population of TEMRA T cells that increases with age, in particular in the CD8+ compartment, is highly oligoclonal with single clonotypes reaching frequencies of up to 1% in the peripheral blood compartment”

    From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Henson et al., 2012

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 54

  1. Thomas ML: The leukocyte common antigen family. Annu Rev Immunol 1989, 7:339-369.
  2. Charbonneau H, Tonks NK, Walsh KA, Fischer EH: The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase. Proc Natl Acad Sci USA 1988, 85:7182-7186.
  3. Barclay AN, McCall MN: CD45; from alloantigen to mapping of restricted epitopes using recombinant soluble CD45 isoforms. Biochem Soc Trans 1992, 20:161-164.
  4. Akbar AN, Terry L, Timms A, Beverley PC, Janossy G: Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol 1988, 140:2171-2178.
  5. Michie CA, McLean A, Alcock C, Beverley PC: Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature 1992, 360:264-265.
  6. Wills MR, Carmichael AJ, Weekes MP, Mynard K, Okecha G, Hicks R, Sissons JG: Human virus-specific CD8+ CTL clones revert from CD45ROhigh to CD45RAhigh in vivo: CD45RAhighCD8+ T cells comprise both naive and memory cells. J Immunol 1999, 162:7080-7087.
  7. Callan MF, Tan L, Annels N, Ogg GS, Wilson JD, O'Callaghan CA, Steven N, McMichael AJ, Rickinson AB: Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. J Exp Med 1998, 187:1395-1402.
  8. Dunne PJ, Belaramani L, Fletcher JM, Fernandez de Mattos S, Lawrenz M, Soares MV, Rustin MH, Lam EW, Salmon M, Akbar AN: Quiescence and functional reprogramming of Epstein-Barr virus (EBV)-specific CD8+ T cells during persistent infection. Blood 2005, 106:558-565.
  9. Geginat J, Sallusto F, Lanzavecchia A: Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells. J Exp Med 2001, 194:1711-1719.
  10. Khan N, Shariff N, Cobbold M, Bruton R, Ainsworth JA, Sinclair AJ, Nayak L, Moss PA: Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol 2002, 169:1984-1992.
  11. Wills MR, Okecha G, Weekes MP, Gandhi MK, Sissons PJ, Carmichael AJ: Identification of naive or antigen-experienced human CD8(+) T cells by expression of costimulation and chemokine receptors: analysis of the human cytomegalovirus-specific CD8(+) T cell response. J Immunol 2002, 168:5455-5464.
  12. Libri V, Azevedo RI, Jackson SE, Di Mitri D, Lachmann R, Fuhrmann S, Vukmanovic-Stejic M, Yong K, Battistini L, Kern F et al.: Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4(+) CD45RA(+) CD27(S) T cells: the potential involvement of interleukin-7 in this process. Immunology 2011, 132:326-339.
  13. Derhovanessian E, Maier AB, Hahnel K, Beck R, de Craen AJ, Slagboom EP, Westendorp RG, Pawelec G: Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans. J Gen Virol 2011, 92:2746-2756.
  14. Geginat J, Lanzavecchia A, Sallusto F: Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines. Blood 2003, 101:4260-4266.
  15. Appay V, Dunbar PR, Callan M, Klenerman P, Gillespie GM, Papagno L, Ogg GS, King A, Lechner F, Spina CA et al.: Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 2002, 8:379-385.
  16. Koch S, Larbi A, Derhovanessian E, Ozcelik D, Naumova E, Pawelec G: Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun Ageing 2008, 5:6.
  17. Henson SM, Franzese O, Macaulay R, Libri V, Azevedo RI, Kiani- Alikhan S, Plunkett FJ, Masters JE, Jackson S, Griffiths SJ et al.: KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells. Blood 2009, 113:6619-6628.
  18. Di Mitri D, Azevedo RI, Henson SM, Libri V, Riddell NE, Macaulay R, Kipling D, Soares MV, Battistini L, Akbar AN: Reversible senescence in human CD4+CD45RA+CD27S memory T cells. J Immunol 2011, 187:2093-2100.
  19. Faragher RG, Kipling D: How might replicative senescence contribute to human ageing? Bioessays 1998, 20:985-991.
  20. Wallace DL, Masters JE, De Lara CM, Henson SM, Worth A, Zhang Y, Kumar SR, Beverley PC, Akbar AN, Macallan DC: Human cytomegalovirus-specific CD8(+) T-cell expansions contain long-lived cells that retain functional capacity in both young and elderly subjects. Immunology 2011, 132:27-38.
  21. Weng NP, Levine BL, June CH, Hodes RJ: Regulated expression of telomerase activity in human T lymphocyte development and activation. J Exp Med 1996, 183:2471-2479.
  22. Plunkett FJ, Franzese O, Belaramani LL, Fletcher JM, Gilmour KC, Sharifi R, Khan N, Hislop AD, Cara A, Salmon M et al.: The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome. Mech Ageing Dev 2005, 126:855-865.
  23. Plunkett FJ, Franzese O, Finney HM, Fletcher JM, Belaramani LL, Salmon M, Dokal I, Webster D, Lawson AD, Akbar AN: The loss of telomerase activity in highly differentiated CD8+CD28-CD27S T cells is associated with decreased Akt (Ser473) phosphorylation. J Immunol 2007, 178:7710-7719.
  24. Romero P, Zippelius A, Kurth I, Pittet MJ, Touvrey C, Iancu EM, Corthesy P, Devevre E, Speiser DE, Rufer N: Four functionally distinct populations of human effector-memory CD8+ T lymphocytes. J Immunol 2007, 178:4112-4119.
  25. Hamann D, Baars PA, Rep MH, Hooibrink B, Kerkhof-Garde SR, Klein MR, van Lier RA: Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med 1997, 186:1407-1418.
  26. Hislop AD, Gudgeon NH, Callan MF, Fazou C, Hasegawa H, Salmon M, Rickinson AB: EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J Immunol 2001, 167:2019-2029.
  27. Lachmann R, Bajwa M, Vita S, Smith H, Cheek E, Akbar A, Kern F: Polyfunctional T cells accumulate in large human cytomegalovirus-specific T cell responses. J Virol 2012, 86:1001-1009.
  28. Ouyang Q, Wagner WM, Voehringer D, Wikby A, Klatt T, Walter S, Muller CA, Pircher H, Pawelec G: Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1). Exp Gerontol 2003, 38:911-920.
  29. von Andrian UH, Mackay CR: T-cell function and migration. Two sides of the same coin. N Engl J Med 2000, 343:1020-1034.
  30. Pittet MJ, Mempel TR: Regulation of T-cell migration and effector functions: insights from in vivo imaging studies. Immunol Rev 2008, 221:107-129.
  31. Miyasaka M, Tanaka T: Lymphocyte trafficking across high endothelial venules: dogmas and enigmas. Nat Rev Immunol 2004, 4:360-370.
  32. Remmerswaal EB, Havenith SH, Idu MM, van Leeuwen EM, van Donselaar KA, Ten Brinke A, van der Bom-Baylon N, Bemelman FJ, van Lier RA, Ten Berge IJ: Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes. Blood 2012, 119:1702-1712.
  33. Hertoghs KM, Moerland PD, van Stijn A, Remmerswaal EB, Yong SL, van de Berg PJ, van Ham SM, Baas F, ten Berge IJ, van Lier RA: Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation. J Clin Invest 2010, 120:4077-4090.
  34. Faint JM, Annels NE, Curnow SJ, Shields P, Pilling D, Hislop AD, Wu L, Akbar AN, Buckley CD, Moss PA et al.: Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics. J Immunol 2001, 167:212-220.
  35. Langeveld M, Gamadia LE, ten Berge IJ: T-lymphocyte subset distribution in human spleen. Eur J Clin Invest 2006, 36:250-256.
  36. Palendira U, Chinn R, Raza W, Piper K, Pratt G, Machado L, Bell A, Khan N, Hislop AD, Steyn R et al.: Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow. Blood 2008, 112:3293-3302.
  37. Herndler-Brandstetter D, Landgraf K, Tzankov A, Jenewein B, Brunauer R, Laschober GT, Parson W, Kloss F, Gassner R, Lepperdinger G et al.: The impact of aging on memory T cell phenotype and function in the human bone marrow. J Leukoc Biol 2012, 91:197-205.
  38. Dunne PJ, Faint JM, Gudgeon NH, Fletcher JM, Plunkett FJ, Soares MV, Hislop AD, Annels NE, Rickinson AB, Salmon M et al.: Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential. Blood 2002, 100:933-940.
  39. Akondy RS, Monson ND, Miller JD, Edupuganti S, Teuwen D, Wu H, Quyyumi F, Garg S, Altman JD, Del Rio C et al.: The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J Immunol 2009, 183:7919-7930.
  40. Sneller MC, Kopp WC, Engelke KJ, Yovandich JL, Creekmore SP, Waldmann TA, Lane HC: IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood. Blood 2011, 118:6845-6848.
  41. Parretta E, Cassese G, Barba P, Santoni A, Guardiola J, Di Rosa F: CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone marrow. J Immunol 2005, 174:7654-7664.
  42. Herndler-Brandstetter D, Landgraf K, Jenewein B, Tzankov A, Brunauer R, Brunner S, Parson W, Kloss F, Gassner R, Lepperdinger G et al.: Human bone marrow hosts polyfunctional memory CD4+ and CD8+ T cells with close contact to IL-15-producing cells. J Immunol 2011, 186:6965-6971.
  43. Sudo T, Ito M, Ogawa Y, Iizuka M, Kodama H, Kunisada T, Hayashi S, Ogawa M, Sakai K, Nishikawa S: Interleukin 7 production and function in stromal cell-dependent B cell development. J Exp Med 1989, 170:333-338.
  44. Wallace DL, Berard M, Soares MV, Oldham J, Cook JE, Akbar AN, Tough DF, Beverley PC: Prolonged exposure of naive CD8+ T cells to interleukin-7 or interleukin-15 stimulates proliferation without differentiation or loss of telomere length. Immunology 2006, 119:243-253.
  45. Soares MV, Borthwick NJ, Maini MK, Janossy G, Salmon M, Akbar AN: IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire. J Immunol 1998, 161:5909-5917.
  46. 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.
  47. Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ: Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 2009, 10:29-37.
  48. Henson SM, Macaulay R, Franzese O, Akbar AN: Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade. Immunology 2012, 135:355-363.
  49. Davis T, Bachler MA, Wyllie FS, Bagley MC, Kipling D: Evaluating the role of p38 MAP kinase in growth of Werner syndrome fibroblasts. Ann N Y Acad Sci 2010, 1197:45-48.
  50. Akbar AN, Vukmanovic-Stejic M: Telomerase in T lymphocytes: use it and lose it? J Immunol 2007, 178:6689-6694.
  51. Parish ST, Wu JE, Effros RB: Modulation of T lymphocyte replicative senescence via TNF-{alpha} inhibition: role of caspase-3. J Immunol 2009, 182:4237-4243.
  52. Akbar AN, Fletcher JM: Memory T cell homeostasis and senescence during aging. Curr Opin Immunol 2005, 17:480-485.
  53. Goronzy JJ, Weyand CM: Rheumatoid arthritis. Immunol Rev 2005, 204:55-73.
  54. Ono K, Han J: The p38 signal transduction pathway: activation and function. Cell Signal 2000, 12:1-13.

Cited by

Sorted by citations

Authors
Henson, S. M., Riddell, N. E., & Akbar, A. N.
Affiliations
University College London (GB)
Corresponding author
Akbar, Arne N
ORCID
Venue
Current Opinion in Immunology
Publisher
Elsevier BV
Published
2012-08
Volume
24
Issue
4
Pages
476-481
ISSN
0952-7915 (ISSN-L)
DOI
10.1016/j.coi.2012.04.001
OpenAlex
W2164575308
Cited by
180
References
8
Citations by year
2026: 13 · 2025: 19 · 2024: 14 · 2023: 20 · 2022: 18 · 2021: 10 · 2020: 16 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 8 · 2015: 10 · 2014: 9 · 2013: 10 · 2012: 1
FWCI
0.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Immunology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Biotechnology and Biological Sciences Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
cellular senescence, cytomegalovirus infection, T cell migration, T cell proliferation, apoptosis
MeSH terms
Humans, T-Lymphocytes, Cellular Senescence, Leukocyte Common Antigens

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review