title: Erythropoietin administration is associated with improved T-cell properties in patients with myelodysplastic syndromes.
abstract: The immune system is impaired in myelodysplastic syndromes (MDS) and plays a role in the pathogenesis of the disease. Here we show effects of recombinant human erythropoietin (rHuEPO) on T cell (CD4+, CD8+and CD4+CD25+) number and function in MDS patients. Healthy (20 subjects), MDS patients without rHuEPO treatment ('MDS', 13), and MDS patients treated with rHuEPO ('MDS+EPO', 17) were examined. CD4+and CD8+T cell numbers were reduced and increased respectively in MDS compared to healthy subjects. EPO treatment normalized these levels. CD4+CD25+cell numbers, lower in MDS, were normalized in MDS+EPO. In vitro activation of CD4+and CD8+cells with phytohemagglutinin as measured by CD69 expression, demonstrated a 7.2 fold increase in CD4+activation vs 13.6 fold for MDS and MDS+EPO respectively (p=0.004); and 10.2 fold (MDS) vs 18.6 fold (MDS+EPO, p<0.003) for CD8+T cells. Expression of the co-stimulatory marker CD28, decreased in CD4+and CD8+T cells in MDS, was normalized in MDS+EPO CD4+T cells. Subgroup analysis of milder disease (WHO RA and RARS) and more advanced disease revealed no difference in CD4+and CD8+T cell numbers. However, the activation of these cells in the RA/RARS subgroup was impaired in EPO-untreated and enhanced in EPO-treated MDS patients. Our data suggest that EPO treatment improves immune abnormalities in MDS and may depend on disease severity.
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Naamit
authors.initials: N
authors.lastname: Deshet-Unger
authors.affiliation: Department of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, 64239, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Oster
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Prutchi-Sagiv
authors.affiliation: Department of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, 64239, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Maaravi
authors.affiliation: Department of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, 64239, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Golishevski
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Drorit
authors.initials: D
authors.lastname: Neumann
authors.affiliation: Department of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, 64239, and Sackler Faculty of Medicine, Tel Aviv University, Israel. Electronic address: moshemt@tlvmc.gov.il.
authors.forename: Moshe
authors.initials: M
authors.lastname: Mittelman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002478:Cells, Cultured; D004921:Erythropoietin / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
chemical_list: D018106:CD28 Antigens; C554270:EPO protein, human; D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: Erythropoietin; Immune modulation; Lymphocytes; Myelodysplastic syndrome; T cells