Journal
BLOOD ADVANCES
Volume 4, Issue 7, Pages 1388-1406Publisher
ELSEVIER
DOI: 10.1182/bloodadvances.2019000699
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Funding
- Medical Research Council [MC_PC_15072]
- Wellcome Trust investigator Award [110091]
- Versus Arthritis fellowship [21745]
- NIHR Manchester Biomedical Research Centre
- Versus Arthritis grant [20385]
- Manchester Academic Health Sciences Centre
- MCCIR (GSK)
- MCCIR (AstraZeneca)
- MCCIR (University of Manchester)
- National Institutes of Health, National Institute on Aging [AI130760]
- American Society for Hematology Junior Scholar Award
- MRC [MC_PC_15072] Funding Source: UKRI
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Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing of NK cells, comparing gene expression in unstimulated and interleukin (IL)-2-activated cells from healthy cytomegalovirus (CMV)-negative donors. Three NK cell subsets resembled well-described populations; CD56(bright)CD16(-), CD56(dim)CD16(+)CD57+(-), and CD56(dim)CD16(+)CD57(+). CD56(di)(m)CD16(+)CD57(-) cells subdivided to include a population with higher chemokine mRNA and increased frequency of killer-cell immunoglobulin-like receptor expression. Three novel human blood NK cell populations were identified: a population of type I interferon-responding NK cells that were CD56(neg); a population exhibiting a cytokine-induced memory-like phenotype, inducfing increased granzyme B mRNA in response to IL-2; and finally, a small population, with low ribosomal expression, downregulation of oxidative phosphorylation, and high levels of immediate early response genes indicative of cellular activation. Analysis of CMV+ donors established that CMV altered the proportion of NK cells in each subset, especially an increase in adaptive NK cells, as well as gene regulation within each subset. Together, these data establish an unexpected diversity in blood NK cells and provide a new framework for analyzing NK cell responses in health and disease.
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