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NDT Advance Access originally published online on December 7, 2004
Nephrology Dialysis Transplantation 2005 20(2):367-376; doi:10.1093/ndt/gfh589
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Nephrol Dial Transplant Vol. 20 No. 2 © ERA–EDTA 2004; all rights reserved

Original Article

Long-term therapy with recombinant human erythropoietin increases CD8+ T-cell apoptosis in haemodialysis patients

Piotr Trzonkowski1, Alicja Debska-Slizien2, Ewa Szmit1, Jolanta Mysliwska1, Katarzyna Szymanska1, Lukasz Hak1, Andrzej Mysliwski1 and Boleslaw Rutkowski2

1 Department of Histology and Immunology, and 2 Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, Poland

Correspondence and offprint requests to: Piotr Trzonkowski, MD, PhD, Department of Histology and Immunology, Medical University of Gdansk, Ul. Debinki 1, 80–211 Gdansk, Poland. Email: ptrzon{at}amg.gda.pl

Background. We intended to assess the intensity of apoptosis in the CD4+ and CD8+ T-lymphocytes of haemodialysis (HD) patients on recombinant human erythropoietin (rHuEpo).

Methods. The expression of Fas, tumour necrosis factor-{alpha} receptors (TNFRI and TNFRII) and the CD28 molecule on lymphocytes was evaluated in 15 HD patients before and during treatment with rHuEpo. In cultures of peripheral blood mononuclear cells (PBMCs) stimulated with rHuEpo, phytohaemagglutinin and camptothecin, our measures of apoptosis were the percentages of cells with subdiploid DNA content and of annexin V-stained cells.

Results, Therapy with rHuEpo did not affect CD4+ T cells but decreased the percentage of CD8+ T cells in peripheral blood. The intensity of apoptosis in both CD4+ and CD8+ T cells at baseline was lower in HD patients than in healthy volunteers, and increased in those treated with rHuEpo. In vitro, rHuEpo did not induce apoptosis in PBMCs. The percentage of CD8+Fas+ T cells was constant, while that of CD8+TNFRI+ cells declined during follow-up. There was an increase in the percentage of CD28+ T cells, mainly in the CD8+ compartment, as early as 1 month after the introduction of rHuEpo.

Conclusions. Treatment with rHupo caused a decline of CD8+ T cells in HD patients, which most probably was mediated via the TNFRI-related apoptotic pathway and was independent of Fas expression. Apoptosis in vitro was not directly influenced by rHuEpo, suggesting that the process in vivo was only initiated by rHuEpo supplementation.

Keywords: apoptosis; erythropoietin; haemodialysis


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P. Trzonkowski, A. Debska-Slizien, A. Mysliwski, and B. Rutkowski
Treatment with recombinant human erythropoietin is associated with rejuvenation of CD8+ T cell compartment in chronic renal failure patients
Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3221 - 3227.
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