Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Dec 24:38:24.
doi: 10.1186/s41232-018-0082-9. eCollection 2018.

The impact of senescence-associated T cells on immunosenescence and age-related disorders

Yuji Fukushima  1 , Nagahiro Minato  2 , Masakazu Hattori  1
Affiliations
Review

The impact of senescence-associated T cells on immunosenescence and age-related disorders

Yuji Fukushima et al. Inflamm Regen. .

Abstract

Immunosenescence is age-associated changes in the immunological functions, including diminished acquired immunity against infection, pro-inflammatory traits, and increased risk of autoimmunity. The proportions of memory-phenotype T cells in the peripheral T cell population steadily increase with age, but the relationship between this change and immunosenescent phenotypes remains elusive. Recently, we identified a minor memory-phenotype CD4+ T cell subpopulation that constitutively expressed PD-1 and CD153 as a bona fide age-dependent T cell population; we termed these cells senescence-associated T (SA-T) cells. SA-T cells exhibit characteristic features of cellular senescence, with defective T cell receptor-mediated proliferation and T cell cytokine production. However, upon T cell receptor stimulation, SA-T cells secrete abundant atypical pro-inflammatory cytokines such as osteopontin and chemokines, reminiscent of the SA-secretory phenotype. In addition to aging, SA-T cells accumulate and cause persistent inflammation in tissues following a wide range of insults including immune complex deposition, metabolic stresses, vascular damages, and tumors. In this review, we summarize the recent understanding of immunosenescence with particular focus on SA-T cells and their role in various age-related disorders.

Keywords: Age-related disorders; Immunosenescence; Osteopontin; Senescence-associated T cells; Thymus.

PubMed Disclaimer

Conflict of interest statement

Not applicableNot applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Increase in MP CD4+ T cells with age. Proportion of MP T cell subsets or total MP CD4+ T cell fraction in the spleens of female B6 mice are shown
Fig. 2
Fig. 2
Properties of SA-T cells
Fig. 3
Fig. 3
Involvement of SA-T cells in the pathogenesis of age-related disorders. a SLE. b Chronic inflammation in VAT
See this image and copyright information in PMC

References

    1. Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018;19:10–9. - PubMed
    1. Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013;14:428–436. doi: 10.1038/ni.2588. - DOI - PMC - PubMed
    1. Hamazaki Y, Sekai M, Minato N. Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution. Immunol Rev. 2016;217:38–55. doi: 10.1111/imr.12412. - DOI - PubMed
    1. Surh CD, Sprent J. Homeostasis of naïve and memory T cells. Immunity. 2008;29:848–862. doi: 10.1016/j.immuni.2008.11.002. - DOI - PubMed
    1. Li G, Yu M, Lee WW, Tsang M, Krishnan E, Weyand CM, Goronzy JJ. Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat Med. 2012;18:1518–1524. doi: 10.1038/nm.2963. - DOI - PMC - PubMed