title: Long-term therapy with recombinant human erythropoietin decreases percentage of CD152(+) lymphocytes in primary glomerulonephritis haemodialysis patients.
abstract: BACKGROUND
  Recombinant human erythropoietin (rHuEpo) may affect the human immune system. The aim of the study was to examine changes in CD4(+) and CD8(+) T-cell subpopulations, the expression of the inhibitory molecule, CD152 on T lymphocytes and the levels of interleukins (IL) 2, 6, 10, 12 and tumour necrosis factor alpha (TNF alpha) in primary glomerulonephritis chronic haemodialysis (HD) patients before and under rHuEpo treatment.
  
  
  METHODS
  Expression of T-cell surface molecules was measured in 14 HD patients ex vivo by flow cytometry of lymphocytes sampled from peripheral blood and in vitro using whole blood cell cultures stimulated either with phytohaemagglutinin (PHA) or with physiological as well as non-physiological doses of rHuEpo. The concentrations of the cytokines were measured in the supernatants from non- or PHA-stimulated cultures using bioassays (IL2, IL6, TNF alpha) or ELISA tests (IL10, IL12).
  
  
  RESULTS
  Compared with findings before the start of rHuEpo therapy the CD4(+)/CD8(+) ratio increased after 1 year of follow-up, whereas the percentage of CD152(+) peripheral blood lymphocytes decreased. The increase of the CD4(+)/CD8(+) ratio was dependent on a decrease of the percentage of CD8(+) cells. The decrease of CD152(+) population affected mainly CD8(+)CD152(+) cells. All these effects became apparent after 6 months of rHuEpo treatment. In vitro stimulation of whole blood cultures revealed that the addition of PHA up-regulated the percentage of CD152(+) lymphocytes, while physiological concentrations of rHuEpo decreased the percentage of CD8(+)152(+) T cells. None of the stimuli used affected the percentage of CD8(+) T cells. The pattern of the cytokines shifted toward TH1 phenotype (increase of IL2 and 12 levels) with a decreased level of proinflammatory cytokines (decrease of IL6 and TNFalpha levels).
  
  
  CONCLUSIONS
  The observed decrease of CD152(+) lymphocytes together with the decrease of CD8(+) cells may reflect the improved immune response observed in HD patients under rHuEpo treatment.
authors.affiliation: Department of Histology and Immunology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Myśliwska
authors.forename: Alicja
authors.initials: A
authors.lastname: Debska-Slizień
authors.forename: Ewa
authors.initials: E
authors.lastname: Bryl
authors.forename: Dominik
authors.initials: D
authors.lastname: Rachoń
authors.forename: Andrzej
authors.initials: A
authors.lastname: Myśliwski
authors.forename: Bolesław
authors.initials: B
authors.lastname: Rutkowski
mesh_terms: D000069594:Abatacept; D000740:Anemia / Q000209:etiology / Q000628:therapy; D015703:Antigens, CD / Q000097:blood; D000943:Antigens, Differentiation / Q000097:blood*; D016516:CD4-CD8 Ratio; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000097:blood; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D005293:Ferritins / Q000097:blood; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D006397:Hematinics; D018796:Immunoconjugates; D011994:Recombinant Proteins; D014168:Transferrin; D004921:Erythropoietin; D000068817:Epoetin Alfa; D000069594:Abatacept; D005293:Ferritins