4.1 Article

Hemodialysis Patients Display a Declined Proportion of Th2 and Regulatory T Cells in Parallel with a High Interferon-γ Profile

期刊

NEPHRON
卷 136, 期 3, 页码 254-260

出版社

KARGER
DOI: 10.1159/000471814

关键词

Chronic kidney disease; Hemodialysis; Inflammation; T-helper; Forkhead box P3 ( FOXP3); GATA-binding protein 3 (GATA3); Interferon-gamma; Interleukin-4

资金

  1. Karolinska Institutet, Stockholm, Sweden

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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)-., 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-gamma 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-gamma profile. Since this profile is characterized in CVDs, we propose that an imbalance between the inflammatory and antiinflammatory responses may contribute to the pathogenesis of CVD in advanced CKD. (C) 2017 S. Karger AG, Basel

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