Erythropoietin administration is associated with improved T-cell properties in patients with myelodysplastic syndromes

Leuk Res. 2017 Jan:52:20-27. doi: 10.1016/j.leukres.2016.11.002. Epub 2016 Nov 2.

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.

Keywords: Erythropoietin; Immune modulation; Lymphocytes; Myelodysplastic syndrome; T cells.

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD28 Antigens / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / drug effects
  • Cells, Cultured
  • Erythropoietin / administration & dosage*
  • Erythropoietin / immunology
  • Female
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / immunology*
  • Myelodysplastic Syndromes / pathology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*

Substances

  • CD28 Antigens
  • EPO protein, human
  • Recombinant Proteins
  • Erythropoietin