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Evidence of premature immune aging in patients thymectomized during early childhood
Open accessAbstract
While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.
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“These studies showed that, independently from age, reduced thymic function and lower production of naïve T cells, together with the consumption of these cells (e.g., upon activation and differentiation during a viral infection), lead to reduced numbers of naïve T cells [75,76].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [75]
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Cited by
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Immunosenescence: molecular mechanisms and diseases
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“This provides much-needed evidence for the role of thymic involution in human immune system aging.(42) According to the latest studies, thymic rejuvenation does not restore diversity, and we agree that thymic degeneration does not perfectly explain the decline in T-cell receptor (TCR) diversity in humans.”
BackgroundUnderstanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827
The Effect of Age on Thymic Function
Palmer, D. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00316 · Cited by 494
“In one such study which looked at patients 20+ years after thymectomy, the authors observed a decreased proportion of naïve T cells, reduction in TCR diversity and noted that such changes were more marked in individuals infected with Cytomegalovirus (22).”
BackgroundBritanova, O. V., Putintseva, E. V., Shugay, M., Merzlyak, E. M., Turchaninova, M. A., Staroverov, D. B., Bolotin, D. A., Lukyanov, S., Bogdanova, E. A., Mamedov, I. Z., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302064 · Cited by 465
“Such an association can be explained by the improved immunoregulatory function of a more diverse CD4+ T cell subset in these individuals, which restrains the generalized inflammation that typically increases with age (58), and provides a better-balanced immune response.”
BackgroundAging of the immune system: Focus on inflammation and vaccination
Pinti, M., Appay, V., Campisi, J., Frasca, D., Fülöp, T., Sauce, D., Larbi, A., Weinberger, B., & Cossarizza, A. (2016) · European Journal of Immunology · doi:10.1002/eji.201546178 · Cited by 439
Self-citation
Metadata
- Authors
- Sauce, D., Larsen, M., Fastenackels, S., Duperrier, A., Keller, M., Grubeck-Loebenstein, B., Ferrand, C., Debré, P., Sidi, D., & Appay, V.
- Affiliations
- Inserm (FR)
- US Forest Service (US)
- Hôpital Necker-Enfants Malades (FR)
- Corresponding author
- Appay, Victor
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2009-10-01
- Volume
- 119
- Issue
- 10
- Pages
- 3070-3078
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2752077
- OpenAlex
- W2153680933
- Cited by
- 278
- References
- 57
- Citations by year
- 2026: 16 · 2025: 11 · 2024: 18 · 2023: 14 · 2022: 15 · 2021: 16 · 2020: 15 · 2019: 11 · 2018: 14 · 2017: 14 · 2016: 17 · 2015: 12 · 2014: 11 · 2013: 22 · 2012: 22
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Oesterreichisches Musiklexikon online (Institut für kunst- und musikhistorische Forschungen der Österreichischen Akademie der Wissenschaften) (submittedVersion, other-oa)
- Austrian Biographical Dictionary (Austrian Academy of Sciences) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Funders
- Sidaction
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- thymectomy, thymus, T cell compartment, naive T cells, cytomegalovirus infection, CMV-specific T-cell responses, T cell exhaustion, congenital heart surgery, CD4+ T cells, CD8+ T cells
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Preschool, Cytomegalovirus Infections, Humans, Immune System, Infant, Newborn, Middle Aged, Thymectomy, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Cytokines, CD8-Positive T-Lymphocytes, Young Adult
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