CD45 Isoform Profile Identifies Natural Killer (NK) Subsets with Differential Activity

Abstract : The leucocyte-specific phosphatase CD45 is present in two main isoforms: the large CD45RA and the short CD45RO. We have recently shown that distinctive expression of these isoforms distinguishes natural killer (NK) populations. For example, co-expression of both isoforms identifies in vivo the anti tumor NK cells in hematological cancer patients. Here we show that low CD45 expression associates with less mature, CD56 bright , NK cells. Most NK cells in healthy human donors are CD45RA + CD45RO-. The CD45RA-RO + phenotype , CD45RO cells, is extremely uncommon in B or NK cells, in contrast to T cells. However , healthy donors possess CD45RA dim RO-(CD45RA dim cells), which show immature markers and are largely expanded in hematopoietic stem cell transplant patients. Blood borne cancer patients also have more CD45RA dim cells that carry several features of immature NK cells. However, and in opposition to their association to NK cell progenitors, they do not proliferate and show low expression of the transferrin receptor protein 1/CD71, suggesting low metabolic activity. Moreover, CD45RA dim cells properly respond to in vitro encounter with target cells by degranulating or gaining CD69 expression. In summary, they are quies-cent NK cells, with low metabolic status that can, however, respond after encounter with target cells.
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Ewelina Krzywinska, Amélie Cornillon, Nerea Allende-Vega, Dang-Nghiem Vo, Céline René, et al.. CD45 Isoform Profile Identifies Natural Killer (NK) Subsets with Differential Activity. PLoS ONE, Public Library of Science, 2016, 11 (4), pp.e0150434. ⟨10.1371/journal.pone.0150434⟩. ⟨inserm-01867110⟩

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