Adaptive NK cells can persist in patients with GATA2 mutation

depleted of stem and progenitor cells

Heinrich Schlums, et al.

Blood. 2017;129(14):1927-1939

Speaker: Yi-Ru Chen (陳奕如)                       Time: 13:10~14:00, Sep 20, 2017

Commentator: Dr. Chi-Chang Shieh (謝奇璋老師)    Place: Room 601

Abstract

GATA-binding protein-2 (GATA-2) is a transcription factor required for hematopoietic stem and progenitor cell (HSPC) survival and proliferation. Heterozygous GATA2 mutation presenting with loss of monocytes, dendritic cells, B cells and natural killer (NK) cells often causes GATA-2 haploinsufficiency¹. Nonetheless, NK cells can persist in some patients who carry GATA2 mutation. Previous studies have shown that cytomegalovirus (CMV) infection would lead to expanding and persisting of NK cells; and further, CMV-associated NK cells displayed features of adaptive T and B cells were considered to be adaptive NK cells². However, the mechanisms of adaptive NK-cell development and homeostasis are poorly understood. In order to investigate the relationship between adaptive NK cells and GATA2 mutation, the authors explored NK-cell phenotype and function in asymptomatic and symptomatic individuals with GATA2 mutation by flow cytometry. They found that peripheral blood NK cells in symptomatic patients lacked expression of the transcription factor, promyelocytic leukemia zinc finger and several intracellular signaling proteins. Moreover, NK cells from patients with GATA2 mutation displayed a similar pattern of cytotoxic granule protein expression observed in adaptive NK cells. The authors also want to figure out the impact of GATA-2 haploinsufficiency on NK-cell differentiation and proliferation. NK cells and lineage-negative (cells which contain HSPCs) cells were sorted out from patients’ blood followed by expanding NK-cell progenitors. The results indicated, no impair of cell proliferation but differentiation. Lin- cells from patients of GATA2 mutation failed to generate NK cell progenitors, with a trend diminishing frequency of NK cells. In conclusion, adaptive NK cells can persist in patients with GATA2 mutation despite having lower HSPCs.

References

1.       Dickinson, R.E., et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 118, 2656-2658 (2011).

2.       Sun, J.C., Beilke, J.N. & Lanier, L.L. Adaptive immune features of natural killer cells. Nature 457, 557 (2009).