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• W2048132371 abstract "Progressive loss of renal function is associated with a dysregulation of circulating T cells that may underlie their impaired T-cell immunity. Here we tested whether end-stage renal disease (ESRD)-related T-cell alterations are compatible with the concept of premature immunological aging. Younger patients (25–45 years old) with ESRD were found to resemble older healthy controls (60–80 years old) as they had a significant loss of naive T cells and a relative increase of memory T cells showing progressive terminal differentiation. A significant decrease in the content of T-cell receptor excision circles and telomere length in patients with ESRD confirmed these phenotypic data. The loss of naive T cells in patients with ESRD was associated with an excessive age-related decrease of recent thymic emigrants, indicating a premature decline in thymic function. Additionally, increased homeostatic proliferation of naive T cells was found in patients with ESRD, similar to that of older healthy individuals, with an increased susceptibility for activation-induced apoptosis. Therefore, both decreased thymic output and increased susceptibility of naive T cells for apoptosis may play a role in the loss of naive T cells in ESRD patients. Thus, our results are compatible with premature aging of the T-cell system of patients with ESRD comparable with that of healthy individuals 20–30 years older. Progressive loss of renal function is associated with a dysregulation of circulating T cells that may underlie their impaired T-cell immunity. Here we tested whether end-stage renal disease (ESRD)-related T-cell alterations are compatible with the concept of premature immunological aging. Younger patients (25–45 years old) with ESRD were found to resemble older healthy controls (60–80 years old) as they had a significant loss of naive T cells and a relative increase of memory T cells showing progressive terminal differentiation. A significant decrease in the content of T-cell receptor excision circles and telomere length in patients with ESRD confirmed these phenotypic data. The loss of naive T cells in patients with ESRD was associated with an excessive age-related decrease of recent thymic emigrants, indicating a premature decline in thymic function. Additionally, increased homeostatic proliferation of naive T cells was found in patients with ESRD, similar to that of older healthy individuals, with an increased susceptibility for activation-induced apoptosis. Therefore, both decreased thymic output and increased susceptibility of naive T cells for apoptosis may play a role in the loss of naive T cells in ESRD patients. Thus, our results are compatible with premature aging of the T-cell system of patients with ESRD comparable with that of healthy individuals 20–30 years older. Progressive loss of renal function is associated with clinical signs of decreased T-cell immunity, such as a poor generation of antigen-specific T cells after vaccination and an increased susceptibility for infections.1.Verkade M.A. van de Wetering J. Klepper M. et al.Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients.Kidney Int. 2004; 66: 614-621Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 2.Litjens N.H. Huisman M. van den Dorpel M. et al.Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients.J Am Soc Nephrol. 2008; 19: 1483-1490Crossref PubMed Scopus (112) Google Scholar Circulating T cells can be characterized as naive (antigen-inexperienced) or memory (antigen-experienced) cells. Differential coexpression of chemokine receptor CCR7 (chemokine (C-C motif) receptor 7) and CD45RO can be used to identify memory T-cell sub-populations that represent an increasing state of differentiation: central-memory (able to home into lymphoid tissues), effector-memory (exerting direct effector functions), and EMRA (highly differentiated effector CD8 T cells lacking CD45RO expression) T cells.3.Litjens N.H. van Druningen C.J. Betjes M.G. Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes.Clin Immunol. 2006; 118: 83-91Crossref PubMed Scopus (110) Google Scholar, 4.Appay V. van Lier R.A. Sallusto F. et al.Phenotype and function of human T lymphocyte subsets: consensus and issues.Cytometry A. 2008; 73: 975-983Crossref PubMed Scopus (529) Google Scholar This increase in differentiation is associated with a progressive increase in expression of the terminal differentiation marker CD57 and loss of the costimulatory molecule CD28 (CD28null) on the surface of T cells.4.Appay V. van Lier R.A. Sallusto F. et al.Phenotype and function of human T lymphocyte subsets: consensus and issues.Cytometry A. 2008; 73: 975-983Crossref PubMed Scopus (529) Google Scholar In aging healthy individuals, the number of circulating T cells only slightly decreases with age, although the thymic output of new T cells (recent thymic emigrants (RTEs)) in the circulation is greatly reduced after the age of 40 years.5.Naylor K. Li G. Vallejo A.N. et al.The influence of age on T cell generation and TCR diversity.J Immunol. 2005; 174: 7446-7452Crossref PubMed Scopus (544) Google Scholar However, T-cell numbers are largely conserved by homeostatic proliferation of both naive and memory T cells, eventually leading to a contracted naive T-cell population but a relatively preserved memory T-cell population. In the very old individuals, a marked increase in naive T-cell proliferation may be observed, a declining CD4/CD8 T-cell ratio, and a relative increase of CD28null T cells.5.Naylor K. Li G. Vallejo A.N. et al.The influence of age on T cell generation and TCR diversity.J Immunol. 2005; 174: 7446-7452Crossref PubMed Scopus (544) Google Scholar, 6.Wikby A. Johansson B. Olsson J. et al.Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study.Exp Gerontol. 2002; 37: 445-453Crossref PubMed Scopus (315) Google Scholar, 7.Wikby A. Maxson P. Olsson J. et al.Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study.Mech Ageing Dev. 1998; 102: 187-198Crossref PubMed Scopus (261) Google Scholar The latter findings are associated with increased mortality and decreased responsiveness to vaccination, and therefore considered an immunological risk profile.8.Goronzy J.J. Fulbright J.W. Crowson C.S. et al.Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals.J Virol. 2001; 75: 12182-12187Crossref PubMed Scopus (331) Google Scholar, 9.Wikby A. Ferguson F. Forsey R. et al.An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans.J Gerontol A Biol Sci Med Sci. 2005; 60: 556-565Crossref PubMed Scopus (289) Google Scholar These observations on physiological aging of the T-cell immune system seem similar to what has been consistently documented in end-stage renal disease (ESRD) patients: lymphopenia, relative expansion of CD28null T cells, and decreased CD4/CD8 ratio.3.Litjens N.H. van Druningen C.J. Betjes M.G. Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes.Clin Immunol. 2006; 118: 83-91Crossref PubMed Scopus (110) Google Scholar, 10.Betjes M.G. Huisman M. Weimar W. et al.Expansion of cytolytic CD4+CD28-T cells in end-stage renal disease.Kidney Int. 2008; 74: 760-767Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 11.Griveas I. Visvardis G. Fleva A. et al.Comparative analysis of immunophenotypic abnormalities in cellular immunity of uremic patients undergoing either hemodialysis or continuous ambulatory peritoneal dialysis.Ren Fail. 2005; 27: 279-282Crossref PubMed Scopus (21) Google Scholar, 12.Yoon J.W. Gollapudi S. Pahl M.V. et al.Naive and central memory T-cell lymphopenia in end-stage renal disease.Kidney Int. 2006; 70: 371-376Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar During T-cell receptor rearrangement within the thymus, T-cell receptor excision circles (TRECs) are formed that remain as circular genomic DNA remnants within the nucleus and are diluted with every T-cell division. A decrease in TREC content in combination with loss of telomere length of T cells therefore reflects the thymic output and replicative history of circulating T cells and can be used to establish the immunological age of T cells.13.Koetz K. Bryl E. Spickschen K. et al.T cell homeostasis in patients with rheumatoid arthritis.Proc Natl Acad Sci USA. 2000; 97: 9203-9208Crossref PubMed Scopus (347) Google Scholar, 14.Zubakov D L.F. van Zelm M.C. Vermeulen J. et al.Estimating human age from T-cell DNA rearrangements.Curr Biol. 2010; 20: R970-971Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar In this study we have tested the hypothesis that the ESRD-related changes of the T-cell compartment are in fact compatible with the concept of premature immunological aging. The clinical and demographical characteristics of ESRD patients and healthy controls (HCs) are shown in Table 1. The variables age, ESRD, dialysis, and the interaction term of age and ESRD were analyzed in a univariate general linear model for their association with T-cell numbers and differentiation patterns (P-values are shown in Table 2). In addition, data on T-cell differentiation of ESRD patients and HCs are shown in Figures 1 and 2.Table 1Clinical and demographic characteristics of patients with end-stage renal disease and healthy controlsEnd-stage renal disease patientsHealthy controlsNumber of individuals137144Age in years52.5±3.9aData are given in means with s.d.53.3±4.0Male67.9.0%63.9%Patients on hemodialysis97—Duration of dialysis in years (median with interquartile range)2.4 (1.5–3.2)—Underlying kidney disease Hypertensive nephropathy43.8%— Primary glomerulopathy14.6%— Diabetic nephropathy8.0%— Polycystic kidney disease8.0%— Reflux nephropathy7.3% Other10.9%— Unknown7.3%—a Data are given in means with s.d. Open table in a new tab Table 2The P-values for the association of ESRD, dialysis, and age with parameters of circulating T cells, analyzed by a univariate general linear modelHemodialysisaESRD with or without hemodialysis.AgebAge categories of young (25–45 years) and old (65–80 years) were used.ESRDAge × ESRDcInteraction term for age and ESRD in the statistical model.CD4 T cells (106/ml)0.81dThe P-values are shown.0.01<0.0010.02CD4 naive T cells (106/ml)0.58<0.01<0.0010.22CD4 memory T cells (106/ml)0.660.28<0.001<0.01% Naive T cells0.270.010.160.82% Central-memory T cells0.130.820.040.22% Effector-memory T cells0.420.03<0.0010.18% CD28null memory T cells0.57<0.001<0.010.95% CD57+ memory T cellsNA0.92<0.01<0.01CD8 T cells (106/ml)0.66<0.01<0.0010.56CD8 naive T cells (106/ml)0.48<0.001<0.0010.02CD8 memory T cells (106/ml)0.700.320.030.02% Naive T cells0.58<0.0010.34<0.001% Central-memory T cells0.40<0.001<0.001<0.001% Effector-memory T cells0.12<0.010.130.01% EMRA T cells0.50<0.0010.040.36% CD28null memory T cells0.69<0.010.020.96% CD57+ memory T cellsNA0.980.260.33Abbreviations: ESRD, end-stage renal disease; NA, not available.a ESRD with or without hemodialysis.b Age categories of young (25–45 years) and old (65–80 years) were used.c Interaction term for age and ESRD in the statistical model.d The P-values are shown. Open table in a new tab Figure 2Composition of peripheral CD4 and CD8 T-cell subsets. The relative distribution of T-cell subsets within the (a) CD4 and (b) CD8 T-cell populations of young (25–45 years, n=60) and old (60–80 years, n=60) end-stage renal disease (ESRD) patients compared with age-matched healthy controls (HCs; young HCs, n=60 and old HCs, n=60) are shown. T-cell subsets are naive T cells, central-memory T cells (CM), effector-memory (EM) T cells, and EMRA CD8 T cells. The black bars represent the young individuals and the white bars correspond to the old individuals. The P-values above the brackets represent the statistical significance for the difference between T-cell subsets of old and young healthy controls or the difference between old and young ESRD patients. The asterisks represent the statistical significance for the difference between T-cell subsets of young HCs compared with young ESRD patients, and T-cell subsets of old HCs compared with old ESRD patients (*P<0.01, **P<0.001, ***P<0.0001). The lower panel shows the percentage of CD28– (CD28null) and CD57+ on (c) memory CD4 and (d) CD8 T cells of young (25–45 years, n=20) and old (60–80 years, n=20) ESRD patients compared with age-matched HCs (young HCs, n=20 and old HCs, n=20). All bars represent means with s.e.m.View Large Image Figure ViewerDownload (PPT) Abbreviations: ESRD, end-stage renal disease; NA, not available. In accordance with previous studies,10.Betjes M.G. Huisman M. Weimar W. et al.Expansion of cytolytic CD4+CD28-T cells in end-stage renal disease.Kidney Int. 2008; 74: 760-767Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 12.Yoon J.W. Gollapudi S. Pahl M.V. et al.Naive and central memory T-cell lymphopenia in end-stage renal disease.Kidney Int. 2006; 70: 371-376Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 15.Betjes M.G. Litjens N.H. Zietse R. Seropositivity for cytomegalovirus in patients with end-stage renal disease is strongly associated with atherosclerotic disease.Nephrol Dial Transplant. 2007; 22: 3298-3303Crossref PubMed Scopus (55) Google Scholar we could not find statistically significant differences in T-cell parameters between patients with or without dialysis. Absolute numbers of CD4 and CD8 T cells showed a significant age-related decline in ESRD patients and HCs (Figure 1a and b). A statistical significant interaction between age and ESRD was only observed for absolute CD4 T-cell numbers (Table 2). The naive CD4 and CD8 T-cell subsets declined with age in both ESRD patients and HCs, with a statistically significant interaction between age and ESRD for only naive CD8 T cells (Table 2). The effect of ESRD on naive T cells was already present in the young age group (Figure 1c and d). The memory CD4 T-cell population decreased significantly in ESRD patients (Figure 1e) with a statistically significant interaction between ESRD and age (Table 2). The young ESRD patients already showed a relative expansion of effector memory CD4 T cells (Tem), which was significantly more pronounced in the old ESRD patients (young versus old ESRD; 36.9 versus 42.4% of CD4 T cells, P<0.0001, Figure 2a). This was reflected by the highly significant P-values for the relation between CD4 Tem and ESRD and for the relation between CD4 Tem and age (Table 2). The absolute number of CD8 memory T cells remained relatively unchanged (Figure 1f), although a significant relation was found with ESRD and the interaction term with age (Table 2). Therefore, the relative decrease of naive T cells was most evident in the CD8 T cells (Figure 2b). Such a difference was expected as it is known that the capacity to expand memory T cells is better for CD8 T cells when compared with CD4 T cells.16.Sauce D. Larsen M. Fastenackels S. et al.Evidence of premature immune aging in patients thymectomized during early childhood.J Clin Invest. 2009; 119: 3070-3078Crossref PubMed Scopus (168) Google Scholar The differentiation of memory CD8 T cells increased with age (Figure 2b), showing a significant increase in the percentage of Tem (19.9–22.5%, P<0.004) and Temra cells (16.2–21.0%, P<0.001) in HCs. In ESRD patients, these changes were observed at an earlier age and reached significantly higher percentages at old age (CD8 Tem 23.7% and Temra 29.1%, P<0.001 compared with young ESRD patients and old HCs). The univariate general linear model confirmed the highly significant association of age (P<0.001) and to a lesser extent ESRD (P=0.04) with the percentage of Temra cells (Table 2). Overall, these data on circulating T cells indicate that age-related changes observed in old HCs are already present in ESRD patients 30 years younger. The percentage of CD28null or CD57+ memory T cells was determined as these markers are associated with progressive differentiation of memory T cells. The percentages of CD28null memory T cells were increased in old HCs and young ESRD patients compared with young HCs, although statistical significance was not reached (Figure 2c and d). However, the old ESRD patients showed a significantly higher percentage of CD28null CD4 (4.3–10.7%, P<0.001) and CD8 T cells (33.3–49.1%, P<0.001). Analysis by a univariate general linear model (Table 2) revealed a highly significant and independent association between age (P<0.001 for CD28null CD4 T cells and P<0.01 for CD28null CD8 T cells) and ESRD (P<0.01 for CD28null CD4 T cells and P=0.02 for CD28null CD8 T cells). Only in the memory CD4 T-cell population of ESRD patients, the percentage of CD57+ cells was significantly increased (Figure 2c), with a statistically significant interaction between age and ESRD (Table 2). The CD28 and CD57 expression patterns on circulating T cells in ESRD patients confirmed the trend of premature aging but appeared less discriminative in comparison with differentiation patterns using CD45RO and CCR7. Dilution of TREC content in the T-cell population (resulting in a higher threshold cycle in the TREC assay) is a result of age-related decrease of thymic T-cell output and T-cell replication history in healthy individuals. We confirmed this relation (Figure 3) and, in addition, a highly significant independent association of both ESRD (P=0.002) and age (P<0.001) with TREC content could be shown by multivariate linear regression analysis. The relative telomere length (RTL) of both CD4 and CD8 T cells decreases with normal aging as a consequence of repetitive T-cell division (Figure 4a and b). Again, the ESRD patients, either young or old, showed a significantly lower CD4 T-cell RTL compared with HCs (Figure 4c). Multivariate linear regression analysis showed a statistically significant independent association of CD4 T-cell RTL with age (P<0.001) and ESRD (P=0.007). The linear regression lines for CD8 T cells in aging healthy individuals and ESRD patients were almost identical to the lines observed in CD4 T cells, but a higher variability of RTL in CD8 T cells was noted. Multivariate linear regression analysis showed a statistically significant independent association of CD8 T-cell RTL with age (P=0.02) but not ESRD (P=0.10).Figure 4Relative telomere length (RTL) of CD4 and CD8 T cells. RTL was assessed by comparing the average telomere length in (a) CD4 and (b) CD8 T-cell populations of end-stage renal disease (ESRD) patients on hemodialysis (closed symbols) and healthy controls (open symbols) to a standardized control. The relation of RTL with age in ESRD patients (n=30) and healthy controls (N=28) is shown by depicting the linear regression lines (P<0.01 for the difference between both lines for CD4 T cells). The RTL of (c) CD4 and (d) CD8 T cells from patients and healthy controls were separated in a young group (age 25–45 years, black bars) and an old group (age 60–80 years, white bars) and statistical significant differences between the groups are shown.View Large Image Figure ViewerDownload (PPT) Based on RTL and TREC content of T cells, the immunological age of ESRD patients was increased by 20–30 years compared with the chronological age-matched HCs. The culprit finding in old age, especially in ESRD patients, is the relative and absolute decrease in circulating naive T cells, particularly in the CD8 T-cell population. The presence of CD31 on naive T cells can be used to identify RTEs (reviewed in Kohler and Thiel17.Kohler S. Thiel A. Life after the thymus: CD31+ and CD31-human naive CD4+ T-cell subsets.Blood. 2009; 113: 769-774Crossref PubMed Scopus (227) Google Scholar). Using this marker we observed a significant age-related decrease in the number of circulating CD31+ naive CD4 and CD8 T cells, which was most evident in old ESRD patients (on average, >70% decrease compared with young ESRD patients and old HCs, Figure 5a and b). The univariate general linear model showed a highly statistical significant association of age, ESRD, and the interaction between age and ESRD (all P-values <0.001) with both CD31+ naive CD4 and CD8 T cells (Table 3).Table 3The association of end-stage renal disease (ESRD) and age with output of recent thymic emigrants (CD31+ naive T cells), percentage of proliferating cells (Ki67+ T cells), and the percentage of cells expressing proapoptotic (CD95) and antiapoptotic (CD279) cell surface moleculesAgeaAge categories of young (25–45 years) and old (65–80 years) were used.ESRDbESRD with or without dialysis.Age × ESRDcInteraction term for age and ESRD in the statistical model.CD31+ naive CD4 T cells (106/ml)<0.001dP-values are shown.<0.001<0.001CD31+ naive CD8 T cells (106/ml)<0.001<0.001<0.001% Ki67+ naive CD4 T cells0.080.010.01% Ki67+ memory CD4 T cells0.920.830.80% CD95+ naive CD4 T cells0.020.070.03% CD95+ memory CD4 T cells0.630.830.56% CD95+ naive CD8 T cells<0.0010.780.18% CD95+ memory CD8 T cells0.560.910.46% CD279+ naive CD4 T cells0.020.310.05% CD279+ memory CD4 T cells0.640.710.74% CD279+ naive CD8 T cells0.220.080.22% CD279+ memory CD8 T cells0.320.2730.62P-values are shown using a univariate general linear model.a Age categories of young (25–45 years) and old (65–80 years) were used.b ESRD with or without dialysis.c Interaction term for age and ESRD in the statistical model.d P-values are shown. Open table in a new tab P-values are shown using a univariate general linear model. The percentage of dividing T cells can be established by staining for the expression of Ki67, an antigen only present in the G1M phase of cell division. Old HCs and ESRD patients had a significant increased percentage of Ki67+ naive CD4 T cells (0.88 and 1.02% respectively, P<0.05 compared with 0.54% in young HCs, Figure 5c). A significant correlation was found between the frequency of Ki67+ naive T cells and the absolute number of naive T cells (R=−0.33, P<0.05), indicating that decreasing numbers of naive T cells were not caused by decreased proliferation, but actually were associated with an increased frequency of dividing naive T cells. ESRD and the interaction term of ESRD and age were both significantly associated with the percentage of Ki67+ naive CD4 T cells (Table 3). No age- or ESRD-related changes were observed in Ki67+ memory T cells (Figure 5d and Table 3). Besides decreased thymic output of naive T cells, increased T-cell apoptosis, as shown by others,18.Meier P. Dayer E. Blanc E. et al.Early T cell activation correlates with expression of apoptosis markers in patients with end-stage renal disease.J Am Soc Nephrol. 2002; 13: 204-212PubMed Google Scholar may underlie the loss of naive T cells in ESRD patients. We observed a similar spontaneous apoptosis in vitro of T cells from ESRD patients compared with HCs (Figure 6a and c). However, a significantly increased activation-induced apoptosis of CD8 and CD4 T cells of ESRD patients compared with HCs (for CD4 T cells, 27.8 versus 22.2%, P=0.04; for CD8 T cells, 32.8 versus 27.6%, P=0.03) was found (Figure 6b and d). This difference could be in particular attributed to a significantly higher apoptosis rate in naive CD4 and CD8 T cells and effector-memory CD4 T cells (Figure 6b and d and Table 4). We could not identify an association between susceptibility of T cells for activation-induced apoptosis and age in both patients and HCs (Table 4). The percentage of CD95-expressing naive CD4 T cells significantly increased with age in HCs (Figure 7a). A statistically significant association of age and the interaction term of age and ESRD, with CD95 expression on naive T cells, was found in the general linear model (Table 3). The percentage of naive CD4 cells expressing the antiapoptotic CD279 molecule (programmed death receptor 1) was unaffected by age and ESRD (Figure 7e–h). The expression of CD95 on naive CD8 T cells was significantly associated with age but not ESRD (Figure 7c and Table 3).Table 4The association of end-stage renal disease (ESRD) and age with the percentage of activation-induced apoptosis in different subsets of circulating T cells, analyzed by a univariate general linear model (P-values are shown)AgeaAge categories of young (25–45 years) and old (65–80 years) were used.ESRDAge × ESRDbInteraction term for age and ESRD in the statistical model.Naive CD4 T cells0.73cThe P-values are shown.0.010.15Central-memory CD4 T cells0.980.330.26Effector-memory CD4 T cells0.600.030.02Naive CD8 T cells0.4900.050.126Central-memory CD8 T cells0.210.270.16Effector-memory CD8 T cells0.100.280.15EMRA CD8 T cells0.0260.210.14a Age categories of young (25–45 years) and old (65–80 years) were used.b Interaction term for age and ESRD in the statistical model.c The P-values are shown. Open table in a new tab Figure 7Sensitivity for apoptosis within CD4 and CD8 T cell subsets. The expression of (a–d) CD95 and (e–h) CD279 on naive and memory CD4 and CD8 T cells is shown for young (25–45 years, n=20) and old (60–80 years, n=20) end-stage renal disease patients on hemodialysis (ESRD young and ESRD old) and compared with age-matched healthy controls (HCs; HCs young, n=20 and HCs old, n=20). The black bars represent the young individuals and the white bars correspond to the old individuals. The results are given in means with s.e.m.View Large Image Figure ViewerDownload (PPT) The expression of CD95 and CD279 on memory CD4 and CD8 T cells was high (on average 90%, Figure 7) and unaffected by age and/or ESRD (Table 3). Collectively, these data show that increased CD95 expression and activation-induced apoptosis of naive T cells in ESRD patients may contribute to loss of naive T cells, irrespective of age. The results of this study show that based on several immunological parameters, such as T-cell numbers and differentiation, TREC content, and RTL of T cells, ESRD is associated with excessive premature aging of the T-cell system over an age range from 20 to 80 years. In accordance with previous studies, we noted that a substantial decline of naive CD4 and CD8 T cells is the key finding of an aged T-cell system. The subsequent homeostatic proliferation of memory T cells is accompanied by increased numbers of T cells that reach the effector-memory and EMRA T-cell stage of development. Numerous studies have shown that these terminally differentiated T-cell phenotypes are associated with increased effector functions (for example, cytokine secretion and cytotoxicity),10.Betjes M.G. Huisman M. Weimar W. et al.Expansion of cytolytic CD4+CD28-T cells in end-stage renal disease.Kidney Int. 2008; 74: 760-767Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 19.Bandres E. Merino J. Vazquez B. et al.The increase of IFN-gamma production through aging correlates with the expanded CD8(+high)CD28(-)CD57(+) subpopulation.Clin Immunol. 2000; 96: 230-235Crossref PubMed Scopus (109) Google Scholar loss of telomere length,20.van de Berg P.J. Griffiths S.J. Yong S.L. et al.Cytomegalovirus infection reduces telomere length of the circulating T cell pool.J Immunol. 2010; 184: 3417-3423Crossref PubMed Scopus (114) Google Scholar and decreased proliferative capacity.21.Vallejo A.N. CD28 extinction in human T cells: altered functions and the program of T-cell senescence.Immunol Rev. 2005; 205: 158-169Crossref PubMed Scopus (272) Google Scholar Although data are few, this association has also been documented in ESRD patients.10.Betjes M.G. Huisman M. Weimar W. et al.Expansion of cytolytic CD4+CD28-T cells in end-stage renal disease.Kidney Int. 2008; 74: 760-767Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 22.Trzonkowski P. Debska-Slizien A. Jankowska M. et al.Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells.Mech Ageing Dev. 2010; 131: 96-104Crossref PubMed Scopus (45) Google Scholar Based on the results of the phenotypical T-cell analysis, it may be concluded that ESRD is associated with excessive premature immunological aging. Next, we performed TREC content analysis and determined relative T-cell telomere length to support this conclusion, as expression of T-cell surface molecules may be influenced by other ESRD-related factors. Both TREC content and RTL showed a decline with age, but again this was significantly greater in ESRD patients when compared with the HCs. In particular, the RTL of ESRD T cells was substantially shorter in all decades, whereas the TREC content at a young age seemed affected to a lesser extent by ESRD. As expected, the number of circulating CD31+ naive T cells, reflecting RTEs, decreased substantially with age in healthy individuals. However, young ESRD patients already had similar low number of RTEs as the old HCs, indicating premature diminished thymic function. The findings are reminiscent of young adults thymectomized during early childhood who show substantial loss of their naive T-cell compartment with accumulation of T cells expressing the aging marker CD57.16.Sauce D. Larsen M. Fastenackels S. et al.Evidence of premature immune a" @default.
• W2048132371 created "2016-06-24" @default.
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• W2048132371 date "2011-07-01" @default.
• W2048132371 modified "2023-10-15" @default.
• W2048132371 title "Premature aging of circulating T cells in patients with end-stage renal disease" @default.
• W2048132371 cites W1518369947 @default.
• W2048132371 cites W1556334181 @default.
• W2048132371 cites W1574493485 @default.
• W2048132371 cites W1652988747 @default.
• W2048132371 cites W1949881454 @default.
• W2048132371 cites W1976789091 @default.
• W2048132371 cites W1976916333 @default.
• W2048132371 cites W1984835077 @default.
• W2048132371 cites W1992990548 @default.
• W2048132371 cites W1995716646 @default.
• W2048132371 cites W1996163802 @default.
• W2048132371 cites W1999924197 @default.
• W2048132371 cites W2016264765 @default.
• W2048132371 cites W2018110777 @default.
• W2048132371 cites W2026340246 @default.
• W2048132371 cites W2028931437 @default.
• W2048132371 cites W2032546353 @default.
• W2048132371 cites W2045427629 @default.
• W2048132371 cites W2059073244 @default.
• W2048132371 cites W2075372159 @default.
• W2048132371 cites W2083295790 @default.
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• W2048132371 cites W2170174785 @default.
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