CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset

S Lopez-Vergès, JM Milush, S Pandey… - Blood, The Journal …, 2010 - ashpublications.org
S Lopez-Vergès, JM Milush, S Pandey, VA York, J Arakawa-Hoyt, H Pircher, PJ Norris
Blood, The Journal of the American Society of Hematology, 2010ashpublications.org
Natural killer (NK) cells are innate immune lymphocytes that express a heterogeneous
repertoire of germline-encoded receptors and undergo a distinct pattern of maturation. CD57
is a marker of terminal differentiation on human CD8+ T cells. Very few newborn or fetal NK
cells express CD57; however, the frequency of CD57-bearing NK cells increases with age.
We assessed the transcriptional, phenotypic, and functional differences between CD57+
and CD57− NK cells within the CD56dim mature NK subset. CD57+ NK cells express a …
Abstract
Natural killer (NK) cells are innate immune lymphocytes that express a heterogeneous repertoire of germline-encoded receptors and undergo a distinct pattern of maturation. CD57 is a marker of terminal differentiation on human CD8+ T cells. Very few newborn or fetal NK cells express CD57; however, the frequency of CD57-bearing NK cells increases with age. We assessed the transcriptional, phenotypic, and functional differences between CD57+ and CD57 NK cells within the CD56dim mature NK subset. CD57+ NK cells express a repertoire of NK-cell receptors, suggestive of a more mature phenotype, and proliferate less when stimulated with target cells and/or cytokines. By contrast, a higher frequency of CD57+ NK cells produced interferon-γ and demonstrated more potent lytic activity when these cells were stimulated through the activating receptor CD16; however, they are less responsive to stimulation by interleukin-12 and interleukin-18. Finally, CD57 expression is induced on CD57CD56dim NK cells after activation by interleukin-2. A combination of a mature phenotype, a higher cytotoxic capacity, a higher sensitivity to stimulation via CD16, with a decreased responsiveness to cytokines, and a decreased capacity to proliferate suggest that CD57+ NK cells are highly mature and might be terminally differentiated.
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