title: Long-term therapy with recombinant human erythropoietin increases CD8+ T-cell apoptosis in haemodialysis patients.
abstract: 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.
authors.affiliation: Department of Histology and Immunology, Medical University of Gdańsk, Ul. Debinki 1, 80-211 Gdańsk, Poland. ptrzon@amg.gda.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.forename: Alicja
authors.initials: A
authors.lastname: Debska-Slizien
authors.forename: Ewa
authors.initials: E
authors.lastname: Szmit
authors.forename: Jolanta
authors.initials: J
authors.lastname: Myśliwska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szymańska
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Hak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Myśliwski
authors.forename: Bolesław
authors.initials: B
authors.lastname: Rutkowski
mesh_terms: D015703:Antigens, CD / Q000097:blood; D017209:Apoptosis / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D004247:DNA / Q000097:blood / Q000235:genetics; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D018655:Lymphocyte Count; D008875:Middle Aged; D011994:Recombinant Proteins; D012016:Reference Values; D006435:Renal Dialysis
chemical_list: D015703:Antigens, CD; D011994:Recombinant Proteins; D004921:Erythropoietin; D004247:DNA