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08-06-2024 | Arteriovenous Fistula | Original Research Paper

Characteristics of T cell premature senescence in maintenance hemodialysis patients

Authors: Wangshu Wu, Ahui Song, Kewei Xie, Jiayue Lu, Bingru Zhao, Cheng Qian, Minzhou Wang, Lulin Min, Wenkai Hong, Huihua Pang, Renhua Lu, Leyi Gu

Published in: Inflammation Research

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Abstract

Background

Uremia-associated immunodeficiency, mainly characterized by T cell dysfunction, exists in patients on maintenance hemodialysis (MHD) and promotes systemic inflammation. However, T cell senescence, one of the causes of T cell dysfunction, has not been clearly revealed yet. In this cross-sectional research, we aimed to study the manifestation of T cell premature senescence in MHD patients and further investigate the associated clinical factors.

Methods

76 MHD patients including 33 patients with cardiovascular diseases (CVD) and 28 patients with arteriovenous fistula (AVF) event history were enrolled in this study. Complementarity determining region 3 (CDR3) of T cell receptor (TCR) was analyzed by immune repertoire sequencing (IR-Seq). CD28- T cell subsets and expression of senescence marker p16 and p21 genes were detected by multicolor flow cytometry and RT-qPCR, respectively.

Results

MHD patients had significantly decreased TCR diversity (P < 0.001), increased CDR3 clone proliferation (P = 0.001) and a left-skewed CDR3 length distribution. The proportion of CD4 + CD28- T cells increased in MHD patients (P = 0.014) and showed a negative correlation with TCR diversity (P = 0.001). p16 but not p21 expression in T cells was up-regulated in MHD patients (P = 0.039). Patients with CVD exhibited increased expression of p16 and p21 genes (P = 0.010 and 0.004, respectively), and patients with AVF events showed further TCR diversity and evenness reduction (P = 0.002 and 0.017, respectively) compared to patients without the comorbidities. Moreover, age, average convection volume, total cholesterol, high-density lipoprotein cholesterol and transferrin saturation were associated with TCR diversity or CD4 + CD28- T cell proportion (P < 0.05).

Conclusions

MHD patients undergo T cell premature senescence characterized by significant TCR diversity reduction and repertoire skew, as well as accumulation of the CD4 + CD28- subset and up-regulation of p16 gene. Patients with CVD or AVF events show higher level of immunosenescence. Furthermore, T cell senescence in MHD patients is associated with blood cholesterol and uremic toxin retention, suggesting potential intervention strategies in the future.
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Metadata
Title
Characteristics of T cell premature senescence in maintenance hemodialysis patients
Authors
Wangshu Wu
Ahui Song
Kewei Xie
Jiayue Lu
Bingru Zhao
Cheng Qian
Minzhou Wang
Lulin Min
Wenkai Hong
Huihua Pang
Renhua Lu
Leyi Gu
Publication date
08-06-2024
Publisher
Springer International Publishing
Published in
Inflammation Research
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-024-01897-2
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