Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo
Open accessAbstract
Age-related decreases in immune function are thought to contribute to the reduced efficacy of vaccinations seen in elderly populations. Our previous in vitro studies demonstrated that naive CD4 T cells from aged TCR-transgenic mice proliferate less than young cells and generate poorly functioning effectors due to decreased IL-2 production. In this current study, we show that this age-related defect in CD4 T cell response also occurs in vivo and that it is correlated with reduced NF-kappa B activation. After transfer to young hosts, CD4 T cells from aged transgenic mice proliferate less and produce reduced levels of IL-2 upon immunization with Ag and alum. Introducing a combination of the inflammatory cytokines TNF-alpha, IL-1, and IL-6, or the use of an adjuvant such as CFA that induces these cytokines, markedly enhanced responses of these aged CD4 T cells, so that they proliferated and produced IL-2 similar to young cells. This enhancement is correlated with the enhanced activation of the transcription factor NF-kappa B in aged cells. We suggest that induction of inflammatory cytokines via adjuvants may enhance the efficacy of vaccinations in elderly populations.
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Development and identification of appropriate adjuvants and cytokines might effectively remedy defects in T cell functions from older adults, both directly and by better activation of DCs.
“The development an identification of appropriate adjuvants and cytokines might effectively remedy defects in T cell functions from older adults, both directly and by better activation of DCs (214–216).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [214]
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- Authors
- Haynes, L., Eaton, S. M., Burns, E. M., Rincon, M., & Swain, S. L.
- Affiliations
- Trudeau Institute (US)
- University of Vermont College of Medicine , Burlington, VT 05405
- Corresponding author
- Haynes, Laura
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-05-01
- Volume
- 172
- Issue
- 9
- Pages
- 5194-5199
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3752606
- OpenAlex
- W1543352581
- Cited by
- 162
- References
- 41
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 6
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG02160, P01AG021600, P01AG01743, P01AG001743, R01AG021054, AG21054)
- 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, CD4+ T cell responses, inflammatory cytokines, NF-κB activation, IL-2 production, TNF-α, interleukin-1, interleukin-6, complete Freund's adjuvant, adjuvants, T cell proliferation, TCR transgenic mice
- MeSH terms
- Aging, Animals, Cell Division, Cells, Cultured, Interleukin-2, Mice, Inbred C57BL, Mice, Transgenic, Peptides, Transcription Factors, CD4-Positive T-Lymphocytes, Down-Regulation, Immunophenotyping, Cytokines, Cellular Senescence, Mice, Knockout, Inflammation Mediators, Adoptive Transfer, Mice
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