The DOI matches its Crossref record; 121 of the 123 references it cites were found in a registry or an index.
Signaling pathways in aged T cells – A reflection of T cell differentiation, cell senescence and host environment
Open accessAbstract
With increasing age, the ability of the immune system to protect against new antigenic challenges or to control chronic infections erodes. Decline in thymic function and cumulating antigenic experiences of acute and chronic infections threaten T cell homeostasis, but insufficiently explain the failing immune competence and the increased susceptibility for autoimmunity. Alterations in signaling pathways in the aging T cells account for many of the age-related defects. Signaling threshold calibrations seen with aging frequently built on mechanisms that are operational in T cell development and T cell differentiation or are adaptations to the changing environment in the aging host. Age-related changes in transcription of receptors and signaling molecules shift the balance towards inhibitory pathways, most dominantly seen in CD8 T cells and to a lesser degree in CD4 T cells. Prominent examples are the expression of negative regulatory receptors of the CD28 and the TNF receptor superfamilies as well the expression of various cytoplasmic and nuclear dual-specific phosphatases.
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“These oligoclonal expanded CD8 + memory T cells are further distinguished in humans by loss of expression of the CD28 co-stimulatory molecule (47,48) and impaired immune function.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [48]
In the citing paper
“Several studies found age-related alterations in T-cell signaling pathways [135], including impairment of PTK phosphorylation, decreased Ca2+ mobilization, and lowered PKC, PI3K and MAPK activation [136].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [136]
In the citing paper
“High ROS levels in T cells can inhibit TCR signaling through lowered expression of TCR/CD3, diminished phosphorylation of ZAP70 and altered Ca2+ mobilization [136].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [136]
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Metadata
- Authors
- Goronzy, J. J., Li, G., Yu, M., & Weyand, C. M.
- Affiliations
- VA Palo Alto Health Care System (US)
- Corresponding author
- Goronzy, Jörg J.
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 24
- Issue
- 5
- Pages
- 365-372
- ISSN
- 1044-5323 (ISSN-L)
- PMC
- PMC3435478
- OpenAlex
- W2028580603
- Cited by
- 134
- References
- 123
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 13 · 2018: 6 · 2017: 7 · 2016: 11 · 2015: 11 · 2014: 9 · 2013: 13 · 2012: 3
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
- National Eye Institute (R01EY011916, R01 EY 11916)
- National Institute of Allergy and Infectious Diseases (R01AI044142, U19-AI57266, R01AI44142, U19AI090019, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527, R01AR42527)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- T cell senescence, signaling pathways, T cell differentiation, T cell homeostasis, CD8+ T cells, CD4+ T cells, CD28, TNF receptor superfamily, immunosenescence, autoimmunity, chronic infection, thymic function
- MeSH terms
- Aging, Animals, Cell Differentiation, Humans, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction, Cellular Senescence
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