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Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance
Open accessAbstract
A key feature of human natural killer (NK) cells, which enables efficient recognition of infected and malignant target cells, is the expression of HLA class I-specific receptors of the KIR and NKG2 gene families. Cell-to-cell variability in receptor expression leads to the formation of complex NK cell repertoires. As outlined here, NK cells go through major changes from newborns to adults characterized by downregulation of the inhibitory NKG2A receptor and concomitant upregulation of KIR family members. This process is completed in young adults, and in the majority of individuals, KIR/NKG2A repertoires remain remarkably stable until old age. Nonetheless, age-related factors have the potential to majorly influence the complexity of NK cell repertoires: Firstly infection with HCMV is associated with major clonal expansions of terminally differentiated NKG2C- and KIR-expressing NK cells in certain individuals. Secondly, ineffective hematopoiesis can lead to immature and less diversified NK cell repertoires as observed in myelodysplastic syndrome (MDS), a malignant disease of the elderly. Thus, whereas in the majority of elderly the NK cell compartment appears to be highly stable in terms of function and phenotype, in a minority of subjects a breakdown of NK cell repertoire diversity is observed that might influence immune surveillance and healthy aging.
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“Thus, many immune cell subsets become hyporesponsive to acute challenges as we age17,19-25.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [21]
In the citing paper
“It should be noted that, in the process of immunosenescence, the activating receptor expression of natural killer (NK) cell markers NKP30, NKP46, etc., is reduced, while the inhibitory receptor expression of KIR, NKG2C, etc., is increased [45, 46].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [45]
In the citing paper
“Two subpopulations of NK cells, immature CD14+CD56dim and mature CD14+CD56bright, are associated with aging and remodeling of mature NK cell subsets, and the reduced expression of activated receptors may promote the escape of NK cells in the elderly [45].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [45]
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Metadata
- Authors
- Manser, A. R., & Uhrberg, M.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Uhrberg, Markus
- ORCID
- Uhrberg, Markus
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2015-08-19
- Volume
- 65
- Issue
- 4
- Pages
- 417-426
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC11028690
- OpenAlex
- W1837057295
- Cited by
- 148
- References
- 56
- Citations by year
- 2026: 19 · 2025: 14 · 2024: 28 · 2023: 19 · 2022: 10 · 2021: 15 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 1
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Krebshilfe (DE) (110351)
- Deutsche Forschungsgemeinschaft (DE) (UH 91/7-1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- natural killer cells, NK cell repertoire, aging, killer cell immunoglobulin-like receptors, NKG2A, NKG2C, HCMV infection, myelodysplastic syndrome, ineffective hematopoiesis, immune surveillance, healthy aging, clonal expansion
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Humans, Immunologic Surveillance, Infant, Infant, Newborn, Killer Cells, Natural, Middle Aged, Myelodysplastic Syndromes, Receptors, Natural Killer Cell
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