Hemodialysis patients display a declined proportion of Th2 and regulatory T cells in parallel with a high interferon-γ profile

L Mansouri, A Nopp, SH Jacobson, B Hylander… - Nephron, 2017 - karger.com
L Mansouri, A Nopp, SH Jacobson, B Hylander, J Lundahl
Nephron, 2017karger.com
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 …
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.
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