CD45 Isoform Profile Identifies Natural Killer (NK) Subsets with Differential Activity.
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.
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.
Ewelina
E
Krzywinska
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.
Amelie
A
Cornillon
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.|Institute for Regenerative Medicine and Biotherapy (IRMB), CHU Montpellier, Montpellier, 34295, France.
Nerea
N
Allende-Vega
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.
Dang-Nghiem
DN
Vo
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.
Celine
C
Rene
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.
Zhao-Yang
ZY
Lu
Centre de Cancérologie de Marseille, Plateforme d'Immunomonitoring en Cancérologie, INSERM, U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM 105, CNRS, UMR7258, Marseille, France.
Christine
C
Pasero
Centre de Cancérologie de Marseille, Plateforme d'Immunomonitoring en Cancérologie, INSERM, U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM 105, CNRS, UMR7258, Marseille, France.
Daniel
D
Olive
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier I, 80 avenue Augustin Fliche, 34295, Montpellier, France.
Nathalie
N
Fegueux
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier I, 80 avenue Augustin Fliche, 34295, Montpellier, France.
Patrick
P
Ceballos
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier I, 80 avenue Augustin Fliche, 34295, Montpellier, France.
Yosr
Y
Hicheri
Institute for Integrative Biology of the Cell (I2BC), Genome Biology Department CNRS - UMR9198, Gif-sur-Yvette, France.
Michal
M
Sobecki
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier I, 80 avenue Augustin Fliche, 34295, Montpellier, France.
Jean-François
JF
Rossi
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier I, 80 avenue Augustin Fliche, 34295, Montpellier, France.|CNRS UMR5235, Université de Montpellier, Montpellier, France.
Guillaume
G
Cartron
INSERM U1183, Université de Montpellier 1, UFR Médecine, Montpellier, France.|Institute for Regenerative Medicine and Biotherapy (IRMB), CHU Montpellier, Montpellier, 34295, France.
Martin
M
Villalba
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology; D045744:Cell Line, Tumor; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D020033:Protein Isoforms; D000099192:CD69 Antigens; C516769:PTPRC protein, human