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

- The immune system is impaired in myelodysplastic syndromes (MDS).
- CD4+, and CD8+, and CD4+CD25+ T cell numbers were abnormal in MDS; erythropoietin (EPO) treatment normalized these levels.
- Activation of CD4+ and CD8+ cells, impaired in MDS group, was improved with EPO treatment.
- CD4+ and CD8+ T cell numbers were similar in mild and more advanced MDS.
- Activation of CD4+ and CD8+ cells is impaired in mild MDS and corrected with EPO treatment.

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.