TY - JOUR
T1 - High-resolution phenotyping identifies NK cell subsets that distinguish healthy children from adults
AU - Mahapatra, Sanjana
AU - Mace, Emily M.
AU - Minard, Charles G.
AU - Forbes, Lisa R.
AU - Vargas-Hernandez, Alexander
AU - Duryea, Teresa K.
AU - Makedonas, George
AU - Banerjee, Pinaki P.
AU - Shearer, William T.
AU - Orange, Jordan S.
N1 - Publisher Copyright:
© 2017 Mahapatra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0181134
DO - 10.1371/journal.pone.0181134
M3 - Article
C2 - 28767726
AN - SCOPUS:85026639646
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 8
M1 - e0181134
ER -