ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Virtual memory CD8⁺ T cells in aging: heterogeneity, bystander protection, inflammatory potential, and inhibitory regulation.Immunity & ageing : I & A · 2026Review
- Aging and vaccines: impact of immunosenescence and inflammaging in vaccine response.Frontiers in aging · 2026Review
- Differentiation-induced reduction in functional diversity restricts the ability of cytomegalovirus-specific CD8 T cells to eliminate virus-infected cells.EBioMedicine · 2026Article
- CMV-specific clonal expansion of Th1, GZMKbioRxiv : the preprint server for biology · 2025Article
- Regulation of CD45 isoforms during human effector and memory CD8 T cell differentiation: Implications for T cell nomenclature.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Heterogeneity of thymic output in the elderly and its association with sex and smoking.JCI insight · 2025Article
- Cytomegalovirus (CMV), oxidative stress, and inflammation: implications for immunosenescence and age-related diseases in the MARK-AGE population.Biogerontology · 2025Article
- Modulating CD226 and PD-(L)1 pathways improves CMV-specific CD8＋T cell responses in the absence of IL-2.BMB reports · 2025Article
- NK-like CD8 T cell: one potential evolutionary continuum between adaptive memory and innate immunity.Clinical and experimental immunology · 2024Review
- Stabilization of the human cytomegalovirus UL136p33 reactivation determinant overcomes the requirement for UL135 for replication in hematopoietic cells.Journal of virology · 2023Article
- Overall avidity declines in TCR repertoires during latent CMV but not EBV infection.Frontiers in immunology · 2023Article
- Transcriptional Analysis of Total CD8Frontiers in immunology · 2022Article
- Significance of bystander T cell activation in microbial infection.Nature immunology · 2022Review
- Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex.Cell reports · 2021Article
- How to Reliably Define Human CD8Cold Spring Harbor perspectives in biology · 2021Review
- Tcf1Nature communications · 2020Article
- In vitro immune responses of human PBMCs against Candida albicans reveals fungal and leucocyte phenotypes associated with fungal persistence.Scientific reports · 2020Article
- Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection.Nature immunology · 2020Article
- Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common.The American journal of medicine · 2020Review
- CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive Function.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 4 countries.
Funding
Abstract
The mechanisms regulating memory CD8(+) T cell function and homeostasis during aging are unclear. CD8(+) effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8(+) T cells with high Ag-binding avidity. In individuals who were HLA-A*0201, CD8(+) T cells that expressed CD45RA and were specific for the pp65 protein (NLVPMVATV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLVPMVATV-specific CD8(+) T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFN-α that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA(-)CD45RO(+) CMV-specific CD8(+) T cells induced CD45RA expression while Ag activated cells remained CD45RO(+). This raises the possibility that non-specific cytokine-driven accumulation of CMV-specific CD8(+)CD45RA(+) T cells with lower Ag-binding avidity may exacerbate the effects of viral reactivation on skewing the T cell repertoire in CMV-infected individuals during aging.
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Registered trials
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