Human CD56dimCD16dimCells As an Individualized Natural Killer Cell Subset

Mathieu Amand, Gilles Iserentant, Aurélie Poli, Marwan Sleiman, Virginie Fievez, Isaura Pilar Sanchez, Nicolas Sauvageot, Tatiana Michel, Nasséra Aouali, Bassam Janji, Claudia Milena Trujillo-Vargas, Carole Seguin-Devaux, Jacques Zimmer*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

81 Citations (Scopus)


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 CD56dimCD16brightsubset 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 CD56brightsubsets 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 CD56dimCD16brightcounterparts. 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 CD56dimCD16brightcells 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 CD56dimCD16brightsubset or placed somewhere else in the NK cell differentiation and maturation pathway.

Original languageEnglish
Article number699
JournalFrontiers in Immunology
Issue numberJUN
Publication statusPublished - 19 Jun 2017


  • CD56 natural killer cells
  • Human
  • Humanized mouse model
  • Natural killer cells
  • Subsets


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