Journal
PLOS ONE
Volume 13, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0208469
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Funding
- Russian Science Foundation [16-15-00309]
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In this work, we analyzed the phenotype and growth of human NK cell clones obtained by the stimulation of individual NK cells with IL-2 and gene-modified K562 feeder cells expressing membrane-bound IL-21 (K562-mblL21). We generated clones from NK cells at distinct differentiation and activation stages, determined by CD56, CD57 and HLA-DR expression levels. Less differentiated CD56(bright) NK cell subsets showed higher cloning efficiency compared with more differentiated CD56(dim) subsets, especially with the CD57(bright) subset. However, clones from the CD56(dim) CD57(-) subset lived longer on average than other subsets. Moreover, several clones with the highest cell numbers were derived from CD56(dim) CD57(-)HLA-DR(-)cells. Most of the clones including those derived from more differentiated CD56(dim) CD57(+/-)NKG2A(-)NK cells showed a less-differentiated NKG2A(+) phenotype. Also, CD57(-) cells were frequently observed in clones derived from CD57(+) NK cells suggesting the loss of CD57 during the cloning process. On the other hand, KIR surface expression once detected for a clone never disappeared entirely, confirming irreversibility of the KIR expression. In summary, we have demonstrated that in specific conditions terminally differentiated CD57(+) human NK cells are able to acquire the CD57(-) phenotype that was previously not observed and, thus, was considered impossible.
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