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Flowchart of flow cytometry analysis to identify CD4 and CD8 T cells. a The flow cytometry picture of lysed peripheral blood including lymphocytes; b the flow cytometry picture of T cells gated from lymphocytes; c the flow cytometry picture of CD4 T cells and CD8 T cells gated from T cells; d the distribution of naïve T cells (CD45RO − CCR7+), central memory T cells (CM, CD45RO+ CCR7+), effector memory T cells (EM, CD45RO + CCR7−), EMRA (CD45RO − CCR7−) gated from CD4 T cells; e the distribution of naïve T cells (CD45RO − CCR7+), central memory T cells (CM, CD45RO+ CCR7+), effector memory T cells (EM, CD45RO + CCR7−), EMRA (CD45RO − CCR7−) gated from CD8 T cells
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Background:
Impaired T cell immune function exists in end-stage renal disease (ESRD) patients. Dialysis treatment may lead to changes in T cell subsets. In the present study, we aimed to identify alterations of T cell phenotypes in ESRD patients, especially in those receiving peritoneal dialysis (PD), and analyze the potential associated factors....
Context in source publication
Context 1
... Diego, CA, USA). FITC-labeled anti-CD45RO (Miltenyi Biotec, Bergisch Gladbach, Germany), and APC/Cy7-labeled anti-CCR7 (BioLegend) was used to identify the differentiation of T lymphocytes. The data were analyzed with a BD LSRFortessa™ flow cytometer (BD Bioscience, San Jose, CA, USA). Flow cytometry was used to assess markers of T cell subsets (Fig. 1). The surface markers CCR7 and CD45RO were used to classify the T cells into subsets: (1) naïve cells (CD45RO-, CCR7+); (2) central memory cells (CD45RO+, CCR7+); (3) effector memory cells (CD45RO+, CCR7-); and (4) effector memory RA cells (CD45RO-, ...
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Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed naïve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count...
Citations
... Changes in the number, subset and effector function of T cells in ESKD and MHD patients have been clearly revealed. This is manifested by a reduction of naïve T cells and an expansion of highly differentiated effector memory T cells, as well as preactivation and tachyphylaxis [7][8][9][10][11][12]. ...
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.
... The proportion of naïve and regulatory T lymphocytes is reduced in CKD. These effects were more prominent in hemodialysis, as compared with peritoneal dialysis patients [1,28,29]. The beneficial effect of peritoneal dialysis was mainly attributed to residual kidney function and the preservation of urine output. ...
Background:
The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients' immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD).
Methods:
The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry.
Results:
The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57- (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27-) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets.
Conclusions:
Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations.
... Furthermore, although not COVID-19-specific, we examined memory T cells in the breakthrough infection group and found that the HD patients had significantly higher central and effector memories than the control group. Upon antigen stimulation, naïve T cells differentiate into long-lived central memory T cells and short-lived effector T cells [20]. Although the presence of moderate COVID-19 cases in HD patients is an important issue to consider, memory immunity may be more strongly induced in HD patients compared to control patients. ...
Coronavirus disease 2019 (COVID-19) following primary immunization (breakthrough infection) has been reported in hemodialysis patients; however, their post-infection immune status remains unclear. We evaluated the humoral and cellular immunity of hemodialysis patients after breakthrough infection. Hemodialysis patients who had received primary immunization against COVID-19 at least six months prior to the study but developed mild/moderate COVID-19 before a booster dose (breakthrough infection group) and hemodialysis patients who were not infected with COVID-19 but received a booster dose (booster immunization group) were recruited. In both groups, SARS-CoV-2 antigen-specific cytokines and IgG levels were measured three weeks after infection or three weeks after receiving a booster dose. Memory T and B cells were also counted in the breakthrough infection group using flow cytometry three weeks after infection. Significantly higher SARS-CoV-2 antigen-specific IgG, IFN-γ, IL-5, TNF-α, and IL-6 levels occurred in the breakthrough infection group compared to the booster immunization group (p = 0.013, 0.039, 0.024, 0.017, and 0.039, respectively). The SARS-CoV-2 antigen-specific IgG and cytokine levels were not significantly different between the two groups. The breakthrough infection group had significantly higher percentages of central and effector memory T cells and regulatory T cells than the comparison group (p = 0.008, 0.031, and 0.026, respectively). Breakthrough infections may induce stronger cellular and humoral immune responses than booster immunizations in hemodialysis patients.
... PD patients show unbalanced lymphocyte metabolism, which is normally tightly regulation by the immune response to glycolysis [19,20], and the expansion and function of T cells may be repressed under high glucose conditions. Malnutrition, accumulation of uremic toxins, and inflammation may lead to the inability to gain adequate nutrients, thereby accelerating the aging process of premature T cells, and causing significant barriers to T cell function in patients with PD [21]. Naïve T cells play a key role in the maintenance of adaptive immunity. ...
Background
The glucose-to-lymphocyte ratio (GLR), a glucose metabolism and systemic inflammatory response parameter, is associated with an adverse prognosis for various diseases. However, the association between serum GLR and prognosis in patients undergoing peritoneal dialysis (PD) is poorly understood.
Methods
In this multi-center cohort study, 3236 PD patients were consecutively enrolled between 1 January 2009 and 31 December 2018. Patients were divided into four groups according to the quartiles of baseline GLR levels (Q1: GLR ≤ 2.91, Q2:2.91 < GLR ≤ 3.91, Q3:3.91 < GLR < 5.59 and Q4: GLR ≥ 5.59). The primary endpoint was all-cause and cardiovascular disease (CVD) related mortality. The correlation between GLR and mortality was examined using Kaplan–Meier and multivariable Cox proportional analyses.
Results
During the follow-up period of 45.93 ± 29.01 months, 25.53% (826/3236) patients died, of whom 31% (254/826) were in Q4 (GLR ≥ 5.59). Multivariable analysis revealed that GLR was significantly associated with all-cause mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p = .019) and CVD mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p = .04). Compared with the Q1 (GLR ≤ 2.91), placement in Q4 was associated with an increased risk of all-cause mortality (adjusted HR: 1.26, 95% CI: 1.02 ∼ 1.56, p = .03) and CVD mortality (adjusted HR 1.76; CI 1.31 ∼ 2.38, p < .001). A nonlinear relationship was found between GLR and all-cause or CVD mortality in patients undergoing PD (p = .032).
Conclusion
A higher serum GLR level is an independent prognostic factor for all-cause and CVD mortality in patients undergoing PD, suggesting that more attention should be paid to GLR.
... A prospective study in chronic dialysis patients during influenza season showed that patients treated with hemodiafiltration demonstrated sustained seroprotection for longer periods in comparison with patients on HD [60]. Some reports outlined that peritoneal dialysis (PD) may better protect from decrease inflammatory status and premature ageing of the immune system in comparison with HD [61][62][63]. However, these data cannot be applied to all transplant candidates, as the immune-nutritional status in PD patients is variable. ...
Kidney transplant candidates and kidney transplant recipients (KTRs) are at particular risk of severe complications of COVID-19 disease. In Western countries, mortality in affected hospitalized KTRs ranges between 19% and 50%. COVID-19 vaccination remains the most important measure to prevent the severity of infection in candidates and recipients of kidney transplant. However, the uraemic condition may affect the vaccine-induced immunity in patients with advanced chronic kidney disease (CKD) and in KTRs. Retention of uraemic toxins, dysbiosis, dysmetabolism, and dialysis can diminish the normal response to vaccination, leading to dysfunction of inflammatory and immune cells. In KTRs the efficacy of vaccines may be reduced by the immunosuppressive medications, and more than half of kidney transplant recipients are unable to build an immune response even after four administrations of anti-COVID-19 vaccines. The lack of antibody response leaves these patients at high risk for SARS-CoV-2 infection and severe COVID-19 disease. The aim of the present review is to focus on the main reasons for the impaired immunological response among candidates and kidney transplant recipients and to highlight some of the present options available to solve the problem.
... Alteration of CD8 + T cell subsets, induced by dialysis modality as well as aging and CMV infection [12,13], could be associated with adverse clinical outcomes. It has been reported that senescence of CD8 + T cells contributes to high risk for cardiovascular disease in CKD patients [14,15], and increased proportion of terminally differentiated memory CD8 + T cells in kidney transplantation patients is associated with a higher risk for skin carcinoma and a lower risk for rejection [16,17]. ...
... Patients on peritoneal dialysis with increased percentage of EM CD8 + T cells were prone to infectious disease, including peritonitis. ESRD patients exhibited the enhanced immunosenescence of CD8 + T cells, which was similar to that seen in healthy elderly people [12,19]. Apart from age, other factors like chronic CMV infection or persistent inflammation could also prompt exhaustion of the CD8 + T cell system and expansion of memory T cell in ESRD patients [12,[19][20][21]. ...
... ESRD patients exhibited the enhanced immunosenescence of CD8 + T cells, which was similar to that seen in healthy elderly people [12,19]. Apart from age, other factors like chronic CMV infection or persistent inflammation could also prompt exhaustion of the CD8 + T cell system and expansion of memory T cell in ESRD patients [12,[19][20][21]. Dialysis could also increase proportion of memory CD8 + T cells in comparison with that of ESRD patients without dialysis, independent of dialysis vintage, and underlying kidney disease [22]. ...
Background:
The immune senescence marked by inflation of memory T cell is established in end-stage renal disease (ESRD) patients with peritoneal dialysis(PD). These patients suffer high incidence of infectious disease, which has been relevant to immune dysfunction. However the association of immune senescence with infection in PD patients is not clear. This prospective study is aim to investigate relationship between proportion of T cell subsets and infection event in patients on PD.
Methods:
We enrolled patients on PD> 6 months from January 1,2016 to December 30,2016 and followed until April 30,2020. Baseline T cell subsets from blood were collected at the time of recruitment. The primary end point was infection event including peritonitis, exit site infection, pneumonia, urinary tract infection and other infection.
Results:
There were 94 patients (46 male) with a mean age of 56.1±14.9 years old enrolled during follow-up period, and 26 patients suffered infection events. Higher proportion of effector memory(EM) CD8+ T cell was found in patients with infection than those without infection. There was no difference of distribution of EM CD8+ T cell between PD-related and non-dialysis infection. Increased level of EM CD8+ T cell was risk factor for first infection event in PD patients.
Conclusion:
High level of EM CD8+ T cell could be a significant predictor of infection event in patients on PD.
... Nongnuch and coworkers demonstrated that Online hemodiafiltration (HDF) increased the percentage of CD38+ Naive CD4+ T cells and CD45RA-CCR7+CD8+ TCM cells compared to those patients treated with HD (9). In addition, hemodialysis induced the shift from a non-aging (CD4+CD28+ T cells) to an aging phenotype (CD4+CD28-T cells) compared to peritoneal dialysis, suggesting that dialysis modality influenced T cell function (34,35). In addition to reduced numbers of T cell subsets, our scRNA-seq data showed decreased expression levels of T-cell identity markers (CD3E, CD3D) and surface receptors of TCR signaling (e.g., TRAV4, CD45, CD3G, ITGA, IL7R) in CD4+ TEM and naive CD4+ T cells. ...
Background
An increased risk of infection, malignancy, and cardiovascular diseases in maintenance hemodialysis patients is associated with hemodialysis-related immunity disturbances. Although defects in T-lymphocyte-dependent immune responses and preactivation of antigen-presenting cells have been documented in hemodialysis patients, the effects of long-term hemodialysis on the transcriptional program and chromosomal accessibility of circulating immune cell subpopulations remain poorly defined.
Methods
We integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to characterize the transcriptome profiles of peripheral mononuclear cells (PBMCs) from healthy controls and maintenance hemodialysis patients. Validation of differentially expressed genes in CD4+ T cells and monocytes were performed by magnetic bead separation and quantitative real-time PCR.
Results
We identified 16 and 15 PBMC subgroups in scRNA-seq and scATAC-seq datasets, respectively. Hemodialysis significantly suppressed the expression levels of T cell receptor (TCR) genes in CD4+ T cell subsets (e.g., TRAV4, CD45, CD3G, CD3D, CD3E) and major histocompatibility complex II (MHC-II) pathway-related genes in monocytes (HLA-DRB1, HLA-DQA2, HLA-DQA1, HLA-DPB1). Downstream pathways of TCR signaling, including PI3K-Akt-mTOR, MAPK, TNF, and NF-κB pathways, were also inhibited in CD4+ T cell subpopulations during the hemodialysis procedure. Hemodialysis altered cellular communication patterns between PBMC subgroups, particularly TGF-TGFBR, HVEM-BTLA, and IL16-CD4 signalings between CD4+ T cells and monocytes. Additionally, we found that hemodialysis inhibited the expression of AP-1 family transcription factors (JUN, JUND, FOS, FOSB) by interfering with the chromatin accessibility profile.
Conclusions
Our study provides a valuable framework for future investigations of hemodialysis-related immune dysregulation and identifies potential therapeutic targets for reconstituting the circulating immune system in maintenance hemodialysis patients.
... After UUO, IS accumulation is aggravated, but its suppression attenuated the progression of renal interstitial fibrosis 33 . Reduced CD4 + /CD8 + ratio is associated with CKD, and the inverted CD4 + /CD8 + ratio is a cause of ESRD 34,35 . AST-120 has been found by other researchers to significantly decrease CD8 + T cells (-33.9% for central memory T cells, and -42.6% for CD8 + naïve T cells), but it does not affect or slightly reduce CD4 + T cells (0 for T helper cell number, and -13.1% for early activated CD4 + T cells) 36 , which are consistent with our findings in this study. ...
Purpose
To explore the potential impact of traditional Chinese herb FuZhengHuaYuJiangZhuTongLuo recipe (FZHY) on renal interstitial fibrosis (RIF) in chronic kidney disease (CKD) at cellular and molecular levels.
Methods
Unilateral ureteral obstruction (UUO) rats were established as the RIF model in vivo. The rats were given intragastric administration with FZHY once a day for consecutive 7, 14 and 21 days, respectively. The renal function parameters and inflammation indicators in kidney tissues were measured using enzyme-linked immunosorbent assay, the CD4⁺/CD8⁺ T cells in peripheral blood was detected using flow cytometry, the renal fibrosis degree was estimated using Masson’s staining, and the fibrosis-related genes’ expression was detected using quantitative polymerase chain reaction, western blotting, and immunohistochemistry analyses.
Results
FZHY prescription reduced the serum creatinine and blood urea nitrogen, decreased the levels of c-reactive protein, interleukin-1, interleukin-6 and tumor necrosis factor-α in kidney tissues, and increased the ratio of CD4⁺/CD8⁺ T cells in peripheral blood. FZHY prescription suppressed the renal tissue fibrosis and reduced the levels of laminin, fibronectin, collagen I and collagen III.
Conclusions
FZHY prescription suppressed the renal fibrosis and improved the condition of “Healthy Qi Deficiency and Evil Qi Excess” in rats with UUO, which may provide an effective method for CKD treatment.
Key words
FZHY; Chronic kidney disease; Fibrosis; Inflammation; CD4 Antigens; CD8 Antigens
... We found that the CD4 T cell percentage was highly significantly lower in HD patients than controls. Xiaoyan et al. [42] confirmed that the CD4 + naïve T cell count was lower and the number of CD8 + naïve T cells was increased in patients on peritoneal dialysis than those on HD. T cell apoptosis due to blood contact with the membrane of the dialyzer may be the reason for the decrease in CD4 T cells. ...
Introduction
The CD4 helper T cell is responsible for humoral, cellular immunity, and inflammation. CD69 may be a sensitive marker indicating that the CD4 T cell is activated. The aim of this study is to determine CD4CD69 T cells for estimating the activation of CD4 T cells and to monitor hemodialysis (HD) outcome.
Participants and methods
Sixty-two HD patients and 50 controls were enrolled in our study. CD3, CD4, CD3CD69, and CD4CD69 T cell percentages were assessed by flow cytometry. Transferrin was determined using ELISA.
Results
The lymphocyte count, the CD3 T cell percentage and CD4 T cell percentage were highly significantly lower, while the CD3CD69 T cell percentage and the CD4CD69 T cell percentage were highly significantly elevated. Mean fluorescence intensity of CD4CD69, 13.89 ± 2.38 (±SD), in the HD group was significantly increased than that of the controls, 13.12 ± 4.93 (±SD) (P < 0.001). On univariate regression analysis, the CD4CD69 T cell was negatively related to albumin [odds ratio (OR), 95% confidence interval (CI): 0.159, 0.037–0.677; P = 0.013) and HD duration (OR, 95% CI: 1.189, 1.098–1.288; P < 0.001) and positively associated with transferrin (OR, 95% CI: 3.015, 1.779–5.108; P < 0.001). Multivariate logistic regression analysis showed that duration of HD and transferrin are independent predictors of the CD4CD69 T cell (OR, 95% CI: 1.187, 1.062–1.327; P = 0.003 and OR, 95% CI: 2.364, 1.004–5.564; P = 0.049, respectively).
Conclusion
CD4CD69 T cell and CD3CD69 T cell percentages were increased in HD patients despite lymphopenia. Reducing the concentration of transferrin and good nutrition may decrease CD4 T cell activation and, consequently, complications in HD patients.
... Although Xiaoyan et al. found no differences in the proportions of CD4+ and CD8+ T lymphocytes between ESRD patients, CKD patients, and healthy controls. The majority of studies indicate that the number of CD4+ and CD8+ cells is diminished in HD patients, suggesting that the HD treatment triggers T lymphocyte apoptosis [17]. CKD inflammation was first identified in the late 1990s, when it was attributed to cardiovascular disease, protein-energy wasting, and mortality [18]. ...
Background
Chronic kidney disease (CKD) is condition characterized by a gradual loss of kidney function, patient with CKD suffering from a variety of immune system defects.Methods
This study looked at Fas, T cell, BCl2, and P53 activity in people with CKD, end stage renal disease (ESRD), and stable controls.ResultsThe CD4+ and CD8+ levels in ESRD patients’ peripheral blood were slightly lower than those in CKD patients. The CKD and ESRD groups had slightly higher Fas and FasL mRNA expression and slightly lower BCl2 mRNA gene expression than the normal control group (P < 0.05). P53 mRNA gene expression was shown to be higher in the patients than in the controls (P < 0.01).ConclusionsESRD patients have a significantly lower number of T-cell subsets than CKD patients this is related to a higher degree of apoptosis in these cells.
