title: Hemodialysis Patients Display a Declined Proportion of Th2 and Regulatory T Cells in Parallel with a High Interferon-γ Profile.
abstract: BACKGROUND
  A high prevalence of cardiovascular diseases (CVDs) and infections in patients with chronic kidney disease (CKD) arises partly due to a high inflammatory state and aberrations in immune cells function. Following in vitro stimulation of leukocytes with different T-cell mitogens, we observed a lower level of interleukin (IL)-2 and IL-10 production in CKD patients. To gain more knowledge as to whether this is the result of an alteration in T-cell function, we investigated the T-cell subsets profile and cytokine production in hemodialysis patients.
  
  
  METHODS
  CD4+ cells were isolated from whole blood of 10 hemodialysis patients and 10 age- and gender-matched healthy controls. Following in vitro stimulation with an antigen-independent T-cell mitogen, Th1, Th2, and regulatory T (Treg) cell subsets were analyzed by flow cytometry through the expression of specific transcription factors. The levels of cytokines, interferon (IFN)-γ, IL-4, and IL-10 were analyzed by enzyme-linked immunosorbent assay in the supernatants.
  
  
  RESULTS
  The proportion of CD4+CD25+FOXP3+ (Treg) and CD4+GATA3+ (Th2) cells was significantly lower in patients compared to healthy controls, while the proportion of CD4+T-bet+ (Th1) cells was similar. Moreover, levels of IL-4 were significantly lower in supernatants from patients, while IFN-γ levels were higher. IL-10 levels did not differ compared to those of the healthy controls.
  
  
  CONCLUSIONS
  Our findings indicate a diminished anti-inflammatory Treg, and Th2 cell profile in hemodialysis patients, accompanied by a high pro-inflammatory IFN-γ profile. Since this profile is characterized in CVDs, we propose that an imbalance between the inflammatory and anti-inflammatory responses may contribute to the pathogenesis of CVD in advanced CKD.
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ladan
authors.initials: L
authors.lastname: Mansouri
authors.forename: Anna
authors.initials: A
authors.lastname: Nopp
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
authors.forename: Britta
authors.initials: B
authors.lastname: Hylander
authors.forename: Joachim
authors.initials: J
authors.lastname: Lundahl
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D007371:Interferon-gamma
keywords: Chronic kidney disease; Forkhead box P3 (FOXP3); GATA-binding protein 3 (GATA3); Hemodialysis; Inflammation; Interferon-γ; Interleukin-4; T-helper