Abstract
Natural killer (NK) cells are critical in immune defense against infected, stressed or transformed cells. Their function is regulated by the heterogeneous expression of a wide array of surface receptors that shape its phenotypic diversity. Although NK cells develop in the bone marrow and secondary lymphoid tissues, substantive differentiation is apparent in the peripheral blood including known age-related variation. In order to gain greater insight into phenotypic and functional variation within peripheral blood NK cells across age groups, we used multi-parametric, polyfunctional flow cytometry to interrogate the NK cell variability in 20 healthy adults and 15 5–10, 11–15 and 16–20 year-old children. We found that the normative ranges in both adults and children displayed great inter-individual variation for most markers. While the expression of several receptors did not differ, among those that did, the majority of the differences existed between adults and the three pediatric groups, rather than among children of different ages. Interestingly, we also identified variation in the individual expression of some markers by sex and ethnicity. Combinatorial analysis of NK cell receptors revealed intermediate subsets between the CD56bright and CD56dim NK cells. Furthermore, on examining the NK cell diversity by age, adults were discovered to have the lowest developmental diversity. Thus, our findings identify previously unappreciated NK cell subsets potentially distinguishing children from adults and suggest functional correlates that may have relevance in age-specific host defense.
Highlights
Natural killer (NK) cells are lymphocytes of the immune system that generally recognize diseased cells without prior antigen sensitization [1]
Activation signals that contribute to this balance can be derived from receptors like natural killer group 2 D (NKG2D) and NKp46, which are relevant in pathogen encounters and anti-tumor immunity [9, 10]
Inhibitory signals which counterbalance activation are mediated via receptors that fall into two main families—NKG2 (NKG2A) and killer-cell immunoglobulin-like receptors (KIR) [11]
Summary
Natural killer (NK) cells are lymphocytes of the immune system that generally recognize diseased cells without prior antigen sensitization [1]. NK cells arise in the bone marrow and further differentiate in secondary lymphoid tissues via a series of coordinated steps which culminate with acquisition of functional competency [2] They comprise 5–15% of peripheral lymphocytes and express a wide array of germline-encoded receptors. NK cells regulate immunity through their release of cytokines and other soluble factors [1] These NK cell functions are mediated by integration of signals via engagement of their receptors, which determines the NK cell response in the absence of antigen-restriction [8]. Inhibitory signals which counterbalance activation are mediated via receptors that fall into two main families—NKG2 (NKG2A) and killer-cell immunoglobulin-like receptors (KIR) [11] These recognize MHC class I molecules in order to identify healthy host cells. NK cell response and a resulting phenotypic distribution is defined by hardwired germline-encoded receptors but can be altered by environmental factors
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