Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age
Open accessAbstract
T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription ( P = 0.002), which inversely correlated with the expression of CD40L ( r = 0.65, P = 0.002), ICOS ( r = 0.57, P = 0.008), and IL-4 ( r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells ( P = 0.003) and the production of ova-specific antibodies ( P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L ( P < 0.001), IL-4 ( P = 0.007), and IL-21 ( P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly ( P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.
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DUSP4 induction and sustained transcription in activated CD4+ memory T cells from humans 65 and older correlates with altered cytokine production and impaired help for B cells.
“One study reported the induction and sustained transcription of DUSP4 in activated CD4 + memory T cells from humans 65 and older, which correlated with their altered cytokine production and an impaired ability to provide help for B cells (87).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [87]
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- Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5561–5562.
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- Authors
- Yu, M., Li, G., Lee, W.-W., Yuan, M., Cui, D., Weyand, C. M., & Goronzy, J. J.
- Affiliations
- VA Palo Alto Health Care System (US)
- Seoul National University (KR)
- Georgia Institute of Technology (US)
- Emory University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-03-20
- Volume
- 109
- Issue
- 15
- Pages
- E879-88
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3326453
- OpenAlex
- W2093324837
- Cited by
- 102
- References
- 68
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 10 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 11 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 6 · 2013: 15 · 2012: 2
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG015043)
- National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
- National Eye Institute (R01EY011916)
- National Institute of Allergy and Infectious Diseases (R01AI044142, R01AI108906, U19AI090019, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- DUSP4, T cell-dependent B cell response, immunosenescence, memory CD4+ T cells, CD40 ligand, ICOS, IL-4, IL-17A, IL-21, B cell differentiation, influenza vaccination
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Animals, B-Lymphocytes, T-Lymphocytes, Helper-Inducer, Humans, Immunologic Memory, Influenza, Human, Lymphocyte Activation, Vaccination, Signal Transduction, Biomarkers, CD4-Positive T-Lymphocytes, Protein Tyrosine Phosphatases, Gene Silencing, Mice, Dual-Specificity Phosphatases, Mitogen-Activated Protein Kinase Phosphatases, Young Adult, Immunity, Humoral
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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