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, CD56bright, 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 CD45RAdimRO- (CD45RAdim cells), which show immature markers and are largely expanded in hematopoietic stem cell transplant patients. Blood borne cancer patients also have more CD45RAdim 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, CD45RAdim cells properly respond to in vitro encounter with target cells by degranulating or gaining CD69 expression. In summary, they are quiescent NK cells, with low metabolic status that can, however, respond after encounter with target cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / immunology
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Antigens, Differentiation, T-Lymphocyte / immunology
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Biomarkers / metabolism
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Bone Marrow / immunology
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Cell Line, Tumor
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Hematopoietic Stem Cell Transplantation / methods
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Humans
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K562 Cells
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Killer Cells, Natural / immunology*
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Lectins, C-Type / immunology
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Leukocyte Common Antigens / immunology*
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Protein Isoforms / immunology*
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Biomarkers
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CD69 antigen
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Lectins, C-Type
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Protein Isoforms
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Leukocyte Common Antigens
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PTPRC protein, human
Grants and funding
All of the authors’ funders are public or charitable organizations. This work was supported by a scientific program from the “Communauté de Travail des Pyrénées” (CTPP5/12 to MV), the charities CIEL, L'Un pour l'Autre and Ensangble (09/2013) (MV), a grant from the European Community Program SUDOE (CLiNK SOE2/P1/E341 to MV and J-FR), an AOI from the CHU Montpellier (N°221826) (GC and MV), a grant from Fondation de France (0057921) and fellowships from the ARC (DOC20121206007) and La Ligue Contre le Cancer (TDKB13362) to EK, and Ministère de l'Enseignement Supérieur et de la Recherche (MESR) (DNV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.