Immunol Cell Biol, 2017, 96(2):212-228

HLA-DR+NK cells are mostly characterized by less mature phenotype and high functional activity

NK cells change their phenotype and functional characteristics during activation. In this work, we searched for a relationship of HLA-DR expression with differentiation stages and functional activity of NK cells ex vivo and stimulated in vitro with IL-2 challenged with gene modified feeder K562 cells expressing membrane-bound IL-21 (K562-mbIL21). This stimulation technique has been described for NK cell expansion in clinical use. We have observed that HLA-DR expression in freshly isolated circulating NK cells was mostly associated with less differentiated CD56brightCD57-cells, although in some individuals it could also be found in terminally differentiated CD57+cells. Ex vivo HLA-DR+NK cells possessed better capacity to produce IFN-γ in response to cytokine stimulation compared to their HLA-DR-counterparts. In vitro activation with IL-2 and K562-mbIL21 induces an increase in HLA-DR-positive NK cell proportion, again mostly among CD56brightCD57-NK cells. This happened in particular due to appearance of HLA-DR+expression de novo in HLA-DR-negative cells. Acquired in vitro HLA-DR expression was associated with NK cell proliferation activity, more intense cytokine-induced IFN-γ production, increased degranulation toward feeder cells, and higher expression of CD86 and NKG2D. Thus, stimulation with IL-2/K562-mbIL21 causes a significant phenotype and functional shift during NK cell activation and expansion. We have observed that HLA-DR expression in freshly isolated circulating NK cells was mostly associated with less differentiated CD56brightCD57-cells, although in some individuals it could also be found in terminally differentiated CD57+cells. Ex vivo HLA-DR+NK cells possessed better capacity to produce IFN-γ in response to cytokine stimulation compared to their HLA-DR-counterparts. In vitro activation with IL-2 and K562-mbIL21 induces an increase in HLA-DR-positive NK cell proportion, again mostly among CD56brightCD57-NK cells.

IBCH: 3170
Ссылка на статью в журнале: http://doi.wiley.com/10.1111/imcb.1032
Кол-во цитирований на 10.2023: 33
Данные статьи проверены модераторами 2017-11-15

Список научных проектов, где отмечена публикация

  1. -Оптимизация NK-клеток для адоптивного переноса при восстановлении пациентов после интенсивной противоопухолевой терапии (January 6, 2016 — December 31, 2018). Kovalenko E.I.. Grant, RSF.