Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Toxins (Basel). 2020 Apr 3;12(4):224. doi: 10.3390/toxins12040224.

Abstract

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.

Keywords: adaptive immunity; chronic kidney disease; immunological ageing; lymphopenia; thymus; uremia.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity*
  • Age Factors
  • Aging / immunology*
  • Aging / metabolism
  • Animals
  • Humans
  • Immunosenescence*
  • Inflammation Mediators / metabolism
  • Kidney / physiopathology
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / physiopathology
  • Oxidative Stress
  • Phenotype
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Thymus Gland / physiopathology
  • Uremia / immunology*
  • Uremia / metabolism
  • Uremia / physiopathology

Substances

  • Inflammation Mediators