Characteristics of T cell premature senescence in maintenance hemodialysis patients.

Autor: Wu W; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Song A; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Xie K; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Lu J; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Zhao B; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Qian C; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Wang M; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Min L; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Hong W; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China., Pang H; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China. panghuihua@126.com., Lu R; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China. lurenhua1977@hotmail.com., Gu L; Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 1, 2nd Floor, Shanghai, 200127, China. guleyi@aliyun.com.
Jazyk: angličtina
Zdroj: Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2024 Aug; Vol. 73 (8), pp. 1299-1309. Date of Electronic Publication: 2024 Jun 08.
DOI: 10.1007/s00011-024-01897-2
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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