Low thymic activity and dendritic cell numbers are associated with the immune response to primary viral infection in elderly humans
Abstract
Immunological competence declines progressively with age, resulting in increased susceptibility of the elderly to infection and impaired responses to vaccines. Underlying mechanisms remain largely obscure as they have been related to complex, individual systemic immune properties that are challenging to investigate. In this study, we explored age-related changes in human immunity during a primary virus infection experimentally induced by immunization with live-attenuated yellow fever (YF) vaccine. Applying detailed serology, advanced FACS analysis, and systems biology, we discovered that aged subjects developed fewer neutralizing Abs, mounted diminished YF-specific CD8+ T cell responses, and showed quantitatively and qualitatively altered YF-specific CD4+ T cell immunity. Among numerous immune signatures, low in vivo numbers of naive CD4+ recent thymic emigrants and peripheral dendritic cells correlated well with reduced acute responsiveness and altered long-term persistence of human cellular immunity to YF vaccination. Hence, we reveal in this article that essential elements of immune responses such as recent thymic emigrants and dendritic cells strongly relate to productive immunity in the elderly, providing a conceivable explanation for diminished responsiveness to vaccination with neoantigens and infection with de novo pathogens in the aged population.
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Reduced primary CD8+ T cell responses are seen in older individuals after live attenuated yellow fever vaccination, manifested as delayed viral clearance and decreased frequencies of activated CD8+ T cells at peak responses.
“Reduced primary CD8+ T cell responses are also seen in older individuals after vaccination with the live attenuated yellow fever vaccine, which manifested as delayed viral clearance and decreased frequencies of activated CD8+ T cells at peak responses”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Schulz et al., 2015
DCs together with naïve T cells represent the most restrictive elements for the immune response to primary viral infections in older people.
“Accordingly, DCs together with naïve T cells represent the most restrictive elements for the immune response to primary viral infections in older people (33).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [33]
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- Authors
- Schulz, A. R., Mälzer, J. N., Domingo, C., Jürchott, K., Grützkau, A., Babel, N., Nienen, M., Jelinek, T., Niedrig, M., & Thiel, A.
- Affiliations
- German Rheumatism Research Centre (DE)
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Robert Koch Institute (DE)
- Berlin Center for Travel and Tropical Medicine , 10117 Berlin ,
- Corresponding author
- Schulz, Axel Ronald
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11
- Volume
- 195
- Issue
- 10
- Pages
- 4699-4711
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2210194898
- Cited by
- 112
- References
- 78
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 14 · 2021: 19 · 2020: 12 · 2019: 10 · 2018: 7 · 2017: 18 · 2016: 8 · 2014: 1 · 2013: 1
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- immunosenescence, aging, yellow fever vaccine, primary viral infection, recent thymic emigrants, dendritic cells, CD4+ T cells, CD8+ T cells, neutralizing antibodies, vaccine response, cell-mediated immunity
- MeSH terms
- Adult, Age Factors, Aged, Aging, Antibodies, Viral, Cell Count, Dendritic Cells, Female, Humans, Immunoglobulin G, Immunocompetence, Male, Middle Aged, Thymus Gland, Vaccination, Vaccines, Attenuated, Viremia, Yellow fever virus, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Lymphocyte Count, Yellow Fever Vaccine, Young Adult, Antibodies, Neutralizing
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 ›
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