Abstract
Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of the relative expression of the adhesion molecule CD56 and the activating receptor CD16. Whereas blood CD56brightCD16dim/− NK cells are classically viewed as immature precursors and cytokine producers, the larger CD56dimCD16bright subset is considered as the most cytotoxic one. In peripheral blood of healthy donors, we noticed the existence of a population of CD56dimCD16dim NK cells that was frequently higher in number than the CD56bright subsets and even expanded in occasional control donors but also in transporter associated with antigen processing-deficient patients, two familial hemophagocytic lymphohistiocytosis type II patients, and several common variable immunodeficiency patients. This population was detected but globally reduced in a longitudinal cohort of 18 HIV-1-infected individuals. Phenotypically, the new subset contained a high percentage of relatively immature cells, as reflected by a significantly stronger representation of NKG2A+ and CD57− cells compared to their CD56dimCD16bright counterparts. The phenotype of the CD56dimCD16dim population was differentially affected by HIV-1 infection as compared to the other NK cell subsets and only partly restored to normal by antiretroviral therapy. From the functional point of view, sorted CD56dimCD16dim cells degranulated more than CD56dimCD16bright cells but less than CD56dimCD16− NK cells. The population was also identified in various organs of immunodeficient mice with a human immune system (“humanized” mice) reconstituted from human cord blood stem cells. In conclusion, the CD56dimCD16dim NK cell subpopulation displays distinct phenotypic and functional features. It remains to be clarified if these cells are the immediate precursors of the CD56dimCD16bright subset or placed somewhere else in the NK cell differentiation and maturation pathway.
Highlights
Natural killer (NK) cells are the founding members of the innate lymphoid cell family
Since the CD56dimCD16dim subset was, among all CD56dim cells, the most affected by HIV-1 infection, we investigated whether the expression of a large set of markers in this population could be differentially affected and distinguish its phenotype as compared to the other natural killer (NK) cell subsets (Figure 4)
We describe CD56dimCD16dim NK cells as a subset of human peripheral blood NK cells and compare it to the other CD56dim populations in terms of phenotype and functions
Summary
Natural killer (NK) cells are the founding members of the innate lymphoid cell family. Considered for decades as exclusively innate lymphocytes, NK cells have been shown to display memory functions as well [2,3,4]. The numerically major subpopulation is CD56dimCD16bright (≥90% of total NK cells) and is frequently described as the most cytotoxic subset, whereas CD56brightCD16dim/− NK cells are abundant cytokine producers. This is still debated, the majority of authors consider the latter as the immature precursor cells of the CD56dimCD16bright population. Peripheral blood contains some CD56dimCD16− and CD56−CD16bright NK cells [9,10,11]
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