End stage renal disease patients have a skewed T cell receptor Vβ repertoire

Huang, Ling; Langerak, Anton W.; Wolvers-Tettero, I. L. M.; Meijers, Ruud W. J.; Baan, Carla C.; Litjens, Nicolle H.R.; Betjes, Michiel G. H.

doi:10.1186/s12979-015-0055-7

Cited by 16 publications

(27 citation statements)

References 34 publications

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“…With different techniques, it was shown that the TCR repertoire of patients with ESRD was skewed because of oligoclonal expansion of specific T cell populations [67,68]. In addition, the PERK phosphorylation pathway in CD4 T cells was disturbed, analogous to what has been described in elderly healthy individuals [69].…”

Section: Renal Failure and Adaptive Immunitymentioning

confidence: 94%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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Progressive loss of renal function is associated with a series of changes of the adaptive immune system which collectively constitute premature immunological ageing. This phenomenon contributes significantly to the mortality and morbidity of end-stage renal disease (ESRD) patients. In this review, the effect of ESRD on the T cell part of the adaptive immune system is highlighted. Naïve T cell lymphopenia, in combination with the expansion of highly differentiated memory T cells, are the hallmarks of immunological ageing. The decreased production of newly formed T cells by the thymus is critically involved. This affects both the CD4 and CD8 T cell compartment and may contribute to the expansion of memory T cells. The expanding populations of memory T cells have a pro-inflammatory phenotype, add to low-grade inflammation already present in ESRD patients and destabilize atherosclerotic plaques. The effect of loss of renal function on the thymus is not reversed after restoring renal function by kidney transplantation and constitutes a long-term mortality risk factor. Promising results from animal experiments have shown that rejuvenation of the thymus is a possibility, although not yet applicable in humans.

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Section: Renal Failure and Adaptive Immunitymentioning

confidence: 94%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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“…Huang et al assessed the factors that may accelerate the TCR β repertoire contraction. They showed that age, CMV infection, and ESKD were significantly and independently associated with a shrinking of the TCR β repertoire (41). The impact of age on the TCR β repertoire concerned only the CD8 + memory T-cell subset but not the naive T-cell subset.…”

Section: Immunological Aspect Of Aging In Kidney Transplant Recipientsmentioning

confidence: 99%

Transplantation of Marginal Organs: Immunological Aspects and Therapeutic Perspectives in Kidney Transplantation

et al. 2020

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“…Blood was drawn from KT-recipients the day before KT. Isolated PBMCs were stored at -150˚C with a minimum amount of 10×10 6 cells per vial until further analysis.…”

Section: Pbmc Isolationmentioning

confidence: 99%

“…Progressive loss of renal function leading to end-stage renal disease (ESRD) is associated with premature ageing of the T-cell system. The pro-inflammatory environment resulting from loss of renal function results in a lower thymic output, increased T-cell differentiation, telomere shortening and skewing of the T cell receptor (TCR) repertoire [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation

Betjes

Litjens

2020

PLoS ONE

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Background The hypothesis was tested that parameters of an aged T-cell compartment associate with the risk for late rejection after kidney transplantation. Methods Recipients of a kidney transplant in the period 2007-2013 were (N = 365) were included. T cells were characterized prior to transplantation by flow cytometry as naive (CD45RO-CCR7 +), central-memory (CD45RO + CCR7 +), effector-memory (CD45RO-CCR7-) or terminally differentiated CD8 + Temra (CD45RO-/CCR7-/CD28-) cells. T cell telomere length and thymic output were assessed prior to transplantation in 202 recipients. Follow-up was until December 2018. The date of the first time of biopsy-proven late rejection (>6 months after transplantation) was used to calculate the rejection-free survival time. Results Fifty cases of biopsy-proven rejection were recorded. Thymic output and T cell telomere length did not associate with late rejection-free survival. However, the percentage and absolute numbers of CD8 + Temra and CD28null CD8 + T cells were significantly lower in patients with late rejection. Specifically, in the highest tertile of percentages of CD28null CD8 + T cells, the cumulative incidence of late rejection at 5 and 10 years was only 5% and 8% compared to 16% and 20% in the middle to lowest tertile (p = 0.002). Multivariate proportional hazard analysis showed that percentage and absolute number of CD28null CD8 + T cells remained significantly associated with late rejection and rejection-related graft loss. Conclusion High numbers of differentiated CD28null CD8 + T cells decrease the risk for late rejection and rejection-related graft loss after kidney transplantation.

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End stage renal disease patients have a skewed T cell receptor Vβ repertoire

Cited by 16 publications

References 34 publications

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Transplantation of Marginal Organs: Immunological Aspects and Therapeutic Perspectives in Kidney Transplantation

High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation

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