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Age-related deregulation of naive T cell homeostasis in elderly humans

AGE volume 33, pages 197–207 (2011)Cite this article

Abstract

Immunosenescence is characterized by phenotypic and functional changes of effector memory T cells. In spite of the well-described senescent defects of these experienced T cells, immune responses to new pathogens are also deeply affected in elderly humans, suggesting that naive T cells could also show age-related defects. It has been reported in both, animal models and humans, alterations of the naive T cell turnover associated to advanced age or low thymic function. However, as far as we know, homeostatic mechanisms involved in the deregulation of naive T cell peripheral dynamics and their consequences are still not well understood. Thus, the aim of our study was to analyze homeostatic parameters of peripheral naive T cells and their relationship with thymic function in young and elderly humans. Our results show that lower naive T cell numbers were associated with a lower thymic function and higher activation and proliferating naive T cell levels. We then analyzed sjTREC numbers and relative telomere length from sorted naive T cells. Our results show that the aberrant activation and proliferation status was related to lower sjTREC numbers (a peripheral proliferation marker) and both, higher CD57 expression levels and shortened telomeres (replicative senescence-related markers). Elderly individuals show a greater contraction of the CD8 naive T cell numbers and all homeostatic alterations were more severe in this compartment. In addition, we found that low functional thymus show a CD4-biased thymocyte production. Taken together, our results suggest a homeostatic deregulation, affecting mostly the naive CD8 T cell subset, leading to the accumulation of age-associated defects in, otherwise, phenotypically naive T cells.

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Acknowledgements

Authors want to thank Dr. Ricardo Pardal and the Laboratorio of Investigaciones Biológicas (LIB) for their priceless help in cell sorting. We also want to thank all the Cardiac surgery staff for their kindness and patience. SFM and ERM have grants from the Fondo de Investigaciones Sanitarias (FIS06/00176 and CP08/00172, respectively). This study is supported by Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD06/0006/0021), Redes Temáticas de Cardiovascular (ISCIII RECAVA RD06/0014), Proyecto de Excelencia, Consejería de Innovación, Ciencia y Empresa (P06-CTS-01579) and Consejería de Salud, Servicio Andaluz de Salud (156/2006 and PI0366/07).

Author information

Affiliations

  1. Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS). Service of Infectious Diseases, Virgen del Rocío University Hospital, Avda. Manuel Siurot s/n, 41013, Seville, Spain

    Sara Ferrando-Martínez, Ezequiel Ruiz-Mateos, Maria del Mar Rodríguez-Méndez & Manuel Leal

  2. Department of Clinical Biochemistry, IBIS/CSIC/University of Seville, Virgen del Rocío University Hospital, Seville, Spain

    Sara Ferrando-Martínez & Maria del Mar Rodríguez-Méndez

  3. Cardiac Surgery, Virgen del Rocio University Hospital, Seville, Spain

    Ana Hernández, Encarnación Gutiérrez & Antonio Ordoñez

Authors
  1. Sara Ferrando-Martínez
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  2. Ezequiel Ruiz-Mateos
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  3. Ana Hernández
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  4. Encarnación Gutiérrez
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  5. Maria del Mar Rodríguez-Méndez
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  6. Antonio Ordoñez
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  7. Manuel Leal
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Corresponding author

Correspondence to Manuel Leal.

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Fig. S1
figure 5

Age-related drop of naive CD4 T cells. B) Differences in percentages of activation (CD38+HLADR+ expressing T cells, dark grey circles), replicative senescence (CD57+ expressing T cells, black circles) and proliferating (Ki67+ expressing T cells, light grey circles) naive CD4 T cells among the age groups. C) sj-TREC levels per naive CD4+ T cell between the age groups (grey circles) and Relative naive CD4+ T cell Telomere Length differences between the age groups (black circles). D) Relationship between peripheral percentage of Naive CD4+ T cells and their Relative Telomere Length. (GIF 0 kb)

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Ferrando-Martínez, S., Ruiz-Mateos, E., Hernández, A. et al. Age-related deregulation of naive T cell homeostasis in elderly humans. AGE 33, 197–207 (2011). https://doi.org/10.1007/s11357-010-9170-8

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  • DOI: https://doi.org/10.1007/s11357-010-9170-8

Keywords

  • Aging
  • Naive T cells
  • Homeostatic proliferation
  • Human thymus
  • Immunosenescence