[PDF][PDF] NKp80 defines a critical step during human natural killer cell development

AG Freud, KA Keller, SD Scoville, BL Mundy-Bosse… - Cell reports, 2016 - cell.com
AG Freud, KA Keller, SD Scoville, BL Mundy-Bosse, S Cheng, Y Youssef, T Hughes…
Cell reports, 2016cell.com
Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through
distinct stages. We identified two SLT lineage (Lin)− CD34− CD117+/− CD94+ CD16−"
stage 4" subsets according to expression of the C-type lectin-like surface-activating receptor,
NKp80: NKp80−(stage" 4a") and NKp80+(stage" 4b"). Whereas stage 4b cells expressed
more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were
cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and …
Summary
Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)CD34CD117+/−CD94+CD16 "stage 4" subsets according to expression of the C-type lectin-like surface-activating receptor, NKp80: NKp80 (stage "4a") and NKp80+ (stage "4b"). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT LinCD34CD117+CD94CD16 "stage 3" cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features.
cell.com