Natural killer cell subsets and receptor expression in peripheral blood mononuclear cells of a healthy Korean population: Reference range, influence of age and sex, and correlation between NK cell receptors and cytotoxicity

Abstract

Background: The purpose of this study was to identify CD56^bright and CD56^dim natural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity.

Materials and methods: We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3^-/CD56^dim and CD3^-/CD56^bright NK cells in whole-blood samples from 122 healthy donors. The expression of these receptors was compared according to age (<30years, n=22, 30-60years, n=73 and >60years, n=27) and gender (male, n=61, female, n=61). NK cell cytotoxicity assays were performed with peripheral blood mononuclear cells (PBMCs) from 18 individuals. The results were compared to the expression levels of NKp30 and NKp46 receptors.

Results: A normal reference range for NK cell receptor expression in two NK cell subsets was established. NKp46 and NKG2D expression gradually decreased with age (p<0.01 and p<0.05, respectively) whereas NK cell proportion and numbers, frequencies of CD56^dim cells, and CD57 expression increased with age (p<0.01 in all cases). Men showed greater NK cell proportion and numbers, frequencies of CD56^dim cells, and CD57 expression compared to those of women (p<0.05 and p<0.001; p<0.01 and p<0.01, respectively). Notably, the expression of NKp46 was negatively correlated with NK cell frequency (r=-0.42, p<0.001). Furthermore, NK cell cytotoxicity was found to positively correlate with NCR expression (p=0.02), but not NK cell proportion (p=0.80).

Conclusion: We have established a profile of NK cell surface receptors for a Korean population, and revealed that age and gender have an effect on the expression of NK cell receptors in the population. Our data might explain why neither NK cell numbers nor proportions correlate with NK cell cytotoxicity.

Keywords: Cytotoxicity; NCR; NK cells; Receptor; Reference range; Subset.