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Published in: Immunity & Ageing 1/2012

Open Access 01-12-2012 | Research

Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients

Authors: Ruud WJ Meijers, Nicolle HR Litjens, Elly A de Wit, Anton W Langerak, Ashley van der Spek, Carla C Baan, Willem Weimar, Michiel GH Betjes

Published in: Immunity & Ageing | Issue 1/2012

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Abstract

Background

End-stage renal disease (ESRD) patients treated with renal replacement therapy (RRT) have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC) content and proliferative history via relative telomere length in ESRD patients not on RRT.

Results

Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8+ T cell differentiation and to reduce CD8+ T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4+ T cells was also noted in young dialysis patients.

Conclusion

Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8+ T cell compartment in particular in young ESRD patients.
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Literature
1.
go back to reference Betjes MG, Langerak AW, van der Spek A, de Wit EA, Litjens NH: Premature aging of circulating T cells in patients with end-stage renal disease. Kidney Int. 2011, 80: 208-217. 10.1038/ki.2011.110.CrossRefPubMed Betjes MG, Langerak AW, van der Spek A, de Wit EA, Litjens NH: Premature aging of circulating T cells in patients with end-stage renal disease. Kidney Int. 2011, 80: 208-217. 10.1038/ki.2011.110.CrossRefPubMed
2.
go back to reference Litjens NH, van Druningen CJ, Betjes MG: Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes. ClinImmunol. 2006, 118: 83-91. Litjens NH, van Druningen CJ, Betjes MG: Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes. ClinImmunol. 2006, 118: 83-91.
3.
go back to reference Litjens NH, Huisman M, van den Dorpel M, Betjes MG: Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients. J Am Soc Nephrol. 2008, 19: 1483-1490. 10.1681/ASN.2007090971.PubMedCentralCrossRefPubMed Litjens NH, Huisman M, van den Dorpel M, Betjes MG: Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients. J Am Soc Nephrol. 2008, 19: 1483-1490. 10.1681/ASN.2007090971.PubMedCentralCrossRefPubMed
4.
go back to reference Verkade MA, de WJ V, Klepper M, Vaessen LM, Weimar W, Betjes MG: Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients. Kidney Int. 2004, 66: 614-621. 10.1111/j.1523-1755.2004.00781.x.CrossRefPubMed Verkade MA, de WJ V, Klepper M, Vaessen LM, Weimar W, Betjes MG: Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients. Kidney Int. 2004, 66: 614-621. 10.1111/j.1523-1755.2004.00781.x.CrossRefPubMed
5.
go back to reference Vanholder R, Ringoir S: Infectious morbidity and defects of phagocytic function in end-stage renal disease: a review. J Am Soc Nephrol. 1993, 3: 1541-1554.PubMed Vanholder R, Ringoir S: Infectious morbidity and defects of phagocytic function in end-stage renal disease: a review. J Am Soc Nephrol. 1993, 3: 1541-1554.PubMed
6.
go back to reference Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D: Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet. 1999, 354: 93-99. 10.1016/S0140-6736(99)06154-1.CrossRefPubMed Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D: Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet. 1999, 354: 93-99. 10.1016/S0140-6736(99)06154-1.CrossRefPubMed
7.
go back to reference Appay V, van Lier RA, Sallusto F, Roederer M: Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A. 2008, 73: 975-983.CrossRefPubMed Appay V, van Lier RA, Sallusto F, Roederer M: Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A. 2008, 73: 975-983.CrossRefPubMed
8.
go back to reference Sallusto F, Geginat J, Lanzavecchia A: Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004, 22: 745-763. 10.1146/annurev.immunol.22.012703.104702.CrossRefPubMed Sallusto F, Geginat J, Lanzavecchia A: Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004, 22: 745-763. 10.1146/annurev.immunol.22.012703.104702.CrossRefPubMed
9.
go back to reference Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, Neuman B, Wurzner R, Grubeck-Loebenstein B: Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol. 2007, 68: 86-90. 10.1016/j.humimm.2006.10.019.CrossRefPubMed Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, Neuman B, Wurzner R, Grubeck-Loebenstein B: Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol. 2007, 68: 86-90. 10.1016/j.humimm.2006.10.019.CrossRefPubMed
10.
go back to reference Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ: The influence of age on T cell generation and TCR diversity. J Immunol. 2005, 174: 7446-7452.CrossRefPubMed Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ: The influence of age on T cell generation and TCR diversity. J Immunol. 2005, 174: 7446-7452.CrossRefPubMed
11.
go back to reference Wikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F: 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: 445-453. 10.1016/S0531-5565(01)00212-1.CrossRefPubMed Wikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F: 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: 445-453. 10.1016/S0531-5565(01)00212-1.CrossRefPubMed
12.
go back to reference Wikby A, Mansson IA, Johansson B, Strindhall J, Nilsson SE: The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age. Biogerontology. 2008, 9: 299-308. 10.1007/s10522-008-9138-6.CrossRefPubMed Wikby A, Mansson IA, Johansson B, Strindhall J, Nilsson SE: The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age. Biogerontology. 2008, 9: 299-308. 10.1007/s10522-008-9138-6.CrossRefPubMed
13.
go back to reference Zubakov D, Liu F, van Zelm MC, Vermeulen J, Oostra BA, van Duijn CM, Driessen GJ, van Dongen JJ, Kayser M, Langerak AW: Estimating human age from T-cell DNA rearrangements. Curr Biol. 2010, 20: R970-971. 10.1016/j.cub.2010.10.022.CrossRefPubMed Zubakov D, Liu F, van Zelm MC, Vermeulen J, Oostra BA, van Duijn CM, Driessen GJ, van Dongen JJ, Kayser M, Langerak AW: Estimating human age from T-cell DNA rearrangements. Curr Biol. 2010, 20: R970-971. 10.1016/j.cub.2010.10.022.CrossRefPubMed
14.
go back to reference Iancu EM, Speiser DE, Rufer N: Assessing ageing of individual T lymphocytes: mission impossible?. Mech Ageing Dev. 2008, 129: 67-78. 10.1016/j.mad.2007.10.005.CrossRefPubMed Iancu EM, Speiser DE, Rufer N: Assessing ageing of individual T lymphocytes: mission impossible?. Mech Ageing Dev. 2008, 129: 67-78. 10.1016/j.mad.2007.10.005.CrossRefPubMed
15.
go back to reference Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M, Wolkowitz O, Mellon S, Blackburn E: Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. J Immunol Methods. 2010, 352: 71-80. 10.1016/j.jim.2009.09.012.PubMedCentralCrossRefPubMed Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M, Wolkowitz O, Mellon S, Blackburn E: Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. J Immunol Methods. 2010, 352: 71-80. 10.1016/j.jim.2009.09.012.PubMedCentralCrossRefPubMed
16.
go back to reference Griveas I, Visvardis G, Fleva A, Papadopoulou D, Mitsopoulos E, Kyriklidou P, Manou E, Ginikopoulou E, Meimaridou D, Paulitou A, Sakellariou G: Comparative analysis of immunophenotypic abnormalities in cellular immunity of uremic patients undergoing either hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail. 2005, 27: 279-282.CrossRefPubMed Griveas I, Visvardis G, Fleva A, Papadopoulou D, Mitsopoulos E, Kyriklidou P, Manou E, Ginikopoulou E, Meimaridou D, Paulitou A, Sakellariou G: Comparative analysis of immunophenotypic abnormalities in cellular immunity of uremic patients undergoing either hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail. 2005, 27: 279-282.CrossRefPubMed
17.
go back to reference Schollmeyer P, Bozkurt F: The immune status of the uremic patient: hemodialysis vs CAPD. Clin Nephrol. 1988, 30 (Suppl 1): S37-40.PubMed Schollmeyer P, Bozkurt F: The immune status of the uremic patient: hemodialysis vs CAPD. Clin Nephrol. 1988, 30 (Suppl 1): S37-40.PubMed
18.
go back to reference Yoon JW, Gollapudi S, Pahl MV, Vaziri ND: Naive and central memory T-cell lymphopenia in end-stage renal disease. Kidney Int. 2006, 70: 371-376. 10.1038/sj.ki.5001550.CrossRefPubMed Yoon JW, Gollapudi S, Pahl MV, Vaziri ND: Naive and central memory T-cell lymphopenia in end-stage renal disease. Kidney Int. 2006, 70: 371-376. 10.1038/sj.ki.5001550.CrossRefPubMed
19.
go back to reference Litjens NH, de Wit EA, Betjes MG: Differential effects of age, cytomegalovirus-seropositivity and end-stage renal disease (ESRD) on circulating T lymphocyte subsets. Immun Ageing. 2011, 8: 2-10.1186/1742-4933-8-2.PubMedCentralCrossRefPubMed Litjens NH, de Wit EA, Betjes MG: Differential effects of age, cytomegalovirus-seropositivity and end-stage renal disease (ESRD) on circulating T lymphocyte subsets. Immun Ageing. 2011, 8: 2-10.1186/1742-4933-8-2.PubMedCentralCrossRefPubMed
20.
go back to reference Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG: Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev. 2000, 121: 187-201.CrossRefPubMed Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG: Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev. 2000, 121: 187-201.CrossRefPubMed
21.
go back to reference Wikby A, Maxson P, Olsson J, Johansson B, Ferguson FG: 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: 187-198. 10.1016/S0047-6374(97)00151-6.CrossRefPubMed Wikby A, Maxson P, Olsson J, Johansson B, Ferguson FG: 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: 187-198. 10.1016/S0047-6374(97)00151-6.CrossRefPubMed
22.
go back to reference Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Lofgren S, Ernerudh J, Pawelec G, Ferguson F, Johansson B: The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev. 2006, 127: 695-704. 10.1016/j.mad.2006.04.003.CrossRefPubMed Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Lofgren S, Ernerudh J, Pawelec G, Ferguson F, Johansson B: The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev. 2006, 127: 695-704. 10.1016/j.mad.2006.04.003.CrossRefPubMed
23.
go back to reference Strindhall J, Nilsson BO, Lofgren S, Ernerudh J, Pawelec G, Johansson B, Wikby A: No Immune Risk Profile among individuals who reach 100 years of age: findings from the Swedish NONA immune longitudinal study. Exp Gerontol. 2007, 42: 753-761. 10.1016/j.exger.2007.05.001.CrossRefPubMed Strindhall J, Nilsson BO, Lofgren S, Ernerudh J, Pawelec G, Johansson B, Wikby A: No Immune Risk Profile among individuals who reach 100 years of age: findings from the Swedish NONA immune longitudinal study. Exp Gerontol. 2007, 42: 753-761. 10.1016/j.exger.2007.05.001.CrossRefPubMed
24.
go back to reference Raskova J, Czerwinski DK, Shea SM, Raska K: Cellular immunity and lymphocyte populations in developing uremia in the rat. J Exp Pathol. 1986, 2: 229-245.PubMed Raskova J, Czerwinski DK, Shea SM, Raska K: Cellular immunity and lymphocyte populations in developing uremia in the rat. J Exp Pathol. 1986, 2: 229-245.PubMed
25.
go back to reference Datta S, Sarvetnick N: Lymphocyte proliferation in immune-mediated diseases. Trends Immunol. 2009, 30: 430-438. 10.1016/j.it.2009.06.002.CrossRefPubMed Datta S, Sarvetnick N: Lymphocyte proliferation in immune-mediated diseases. Trends Immunol. 2009, 30: 430-438. 10.1016/j.it.2009.06.002.CrossRefPubMed
26.
go back to reference Litjens NH, Huisman M, Hijdra D, Lambrecht BM, Stittelaar KJ, Betjes MG: IL-2 producing memory CD4+ T lymphocytes are closely associated with the generation of IgG-secreting plasma cells. JImmunol. 2008, 181: 3665-3673.CrossRef Litjens NH, Huisman M, Hijdra D, Lambrecht BM, Stittelaar KJ, Betjes MG: IL-2 producing memory CD4+ T lymphocytes are closely associated with the generation of IgG-secreting plasma cells. JImmunol. 2008, 181: 3665-3673.CrossRef
27.
go back to reference Fry TJ, Connick E, Falloon J, Lederman MM, Liewehr DJ, Spritzler J, Steinberg SM, Wood LV, Yarchoan R, Zuckerman J: A potential role for interleukin-7 in T-cell homeostasis. Blood. 2001, 97: 2983-2990. 10.1182/blood.V97.10.2983.CrossRefPubMed Fry TJ, Connick E, Falloon J, Lederman MM, Liewehr DJ, Spritzler J, Steinberg SM, Wood LV, Yarchoan R, Zuckerman J: A potential role for interleukin-7 in T-cell homeostasis. Blood. 2001, 97: 2983-2990. 10.1182/blood.V97.10.2983.CrossRefPubMed
28.
go back to reference Schluns KS, Kieper WC, Jameson SC, Lefrancois L: Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol. 2000, 1: 426-432. 10.1038/80868.CrossRefPubMed Schluns KS, Kieper WC, Jameson SC, Lefrancois L: Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol. 2000, 1: 426-432. 10.1038/80868.CrossRefPubMed
29.
go back to reference Hultdin M, Gronlund E, Norrback K, Eriksson-Lindstrom E, Just T, Roos G: Telomere analysis by fluorescence in situ hybridization and flow cytometry. Nucleic Acids Res. 1998, 26: 3651-3656. 10.1093/nar/26.16.3651.PubMedCentralCrossRefPubMed Hultdin M, Gronlund E, Norrback K, Eriksson-Lindstrom E, Just T, Roos G: Telomere analysis by fluorescence in situ hybridization and flow cytometry. Nucleic Acids Res. 1998, 26: 3651-3656. 10.1093/nar/26.16.3651.PubMedCentralCrossRefPubMed
Metadata
Title
Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients
Authors
Ruud WJ Meijers
Nicolle HR Litjens
Elly A de Wit
Anton W Langerak
Ashley van der Spek
Carla C Baan
Willem Weimar
Michiel GH Betjes
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2012
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/1742-4933-9-19

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