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Updated: Jun 5, 2026

A Flow Cytometry-Based Cytotoxicity Assay for the Assessment of Human NK Cell Activity
Published on: August 9, 2017
Age-related changes in natural killer cell receptors from childhood through old age
Aline Almeida-Oliveira1, Monique Smith-Carvalho, Luis Cristovão Porto
1Bone Marrow Transplantation Center (CEMO), National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil. aline.almeida@bio.fiocruz.br
Abstract:
Most studies on natural killer (NK) cells and aging have focused on overall cell numbers and global cytotoxic activity. NK cell functions are controlled by surface receptors belonging to three major families: killer cell immunoglobulin-like receptors (KIRs), natural cytotoxicity receptors (NCRs), and C-type lectins. The expression of these receptors was investigated from childhood through old age in T, NKT- and NK cells and also in the CD56(dim) (cytotoxic) and CD56(bright) (responsible for cytokine production) NK cell subsets. A decrease in the expression of activating receptors (NKp30 and NKp46) was observed in NK cells in elderly individuals. KIR expression was increased only in the CD56(bright) subset. Children presented similar results regarding expression of NKp30 and KIR, but not NKp46. NKG2D expression was decreased in T cells of elderly subjects. Analysis of KIR genotype revealed that KIR2DL5 and KIR2DS3 were significantly associated with old age. Cytotoxic activity was preserved from childhood through old age, suggesting that the increase of the absolute number of CD56(dim), observed in elderly, may represent a compensatory mechanism for the receptor expression alterations. This initial study provides the framework for more focused studies of this subject, which are necessary to determine whether the changing balance of NK receptor expression may influence susceptibility to infectious, inflammatory, and neoplastic diseases.
Insights
Natural killer (NK) cell receptor expression changes with age, with decreased activating receptors in the elderly. Despite these changes, cytotoxic activity is maintained, possibly due to increased CD56(dim) cell numbers.
Area of Science:
- Immunology
- Aging Research
- Cell Biology
Background:
- Natural killer (NK) cell research often focuses on cell numbers and overall cytotoxic activity.
- NK cell function is regulated by surface receptors: killer cell immunoglobulin-like receptors (KIRs), natural cytotoxicity receptors (NCRs), and C-type lectins.
Purpose of the Study:
- To investigate the age-related expression of NK cell surface receptors across different cell types and subsets.
- To analyze the association of specific KIR genotypes with advanced age.
Main Methods:
- Flow cytometry was used to analyze receptor expression (KIRs, NCRs, C-type lectins, NKG2D) on T, NKT, and NK cells (CD56(dim) and CD56(bright) subsets) from childhood to old age.
- KIR genotyping was performed.
Main Results:
- Elderly individuals showed decreased expression of activating NK receptors (NKp30, NKp46) on NK cells and NKG2D on T cells.
- KIR expression increased in the CD56(bright) NK cell subset in the elderly.
- KIR2DL5 and KIR2DS3 genotypes were significantly associated with old age.
- Cytotoxic activity remained preserved across all age groups.
Conclusions:
- Age-associated alterations in NK cell receptor expression occur, particularly a decrease in activating receptors.
- Preserved cytotoxic activity in the elderly may be a compensatory mechanism related to an increased number of CD56(dim) NK cells.
- Further research is needed to understand how these NK receptor expression changes impact disease susceptibility.
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