title: Recombinant human erythropoietin treatment of chronic renal failure patients normalizes altered phenotype and proliferation of CD4-positive T lymphocytes.
abstract: Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4(+) T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4(+) lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4(+) T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4(+)CD95(+), CD4(+)HLA-DR(+) cells, and lower percentages of CD4(+)CD69(+) and CD4(+)CD28(+) cells were observed in both rhEPO-treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4(+)CD28(+) and CD4(+)HLA-DR(+) subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPObeta. CD4(+) lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO-treated patients was similar to that observed in healthy controls. Fewer CD4(+)CD28(+) T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0-->G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4(+) T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.
authors.affiliation: Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Lisowska
authors.forename: Alicja
authors.initials: A
authors.lastname: Debska-Slizien
authors.forename: Monika
authors.initials: M
authors.lastname: Radzka
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Witkowski
authors.forename: Boleslaw
authors.initials: B
authors.lastname: Rutkowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Bryl
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016130:Immunophenotyping / Q000379:methods; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016896:Treatment Outcome; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D023201:CD40 Ligand; D000068817:Epoetin Alfa; D004921:Erythropoietin; D006397:Hematinics; D007155:Immunologic Factors; D037181:Lectins, C-Type; D011994:Recombinant Proteins; D000099192:CD69 Antigens