Impaired T cell proliferation, increased soluble death-inducing receptors and activation-induced T cell death in patients undergoing haemodialysis

Clin Exp Immunol. 2001 Jul;125(1):142-8. doi: 10.1046/j.1365-2249.2001.01590.x.

Abstract

Haemodialysis is a widespread option for end-stage renal disease (ESRD). Long-term success of dialysis is, however, limited by a high rate of serious bacterial and viral infections. We compared T cell functions in ESRD patients undergoing haemodialysis (n = 20), or were not dialysed and received conventional medical treatment (n = 20). Healthy volunteers (n = 15) served as controls. The T cell phenotype was examined by immunofluorescence using fluorochrome-labelled monoclonal antibodies and FACS analysis. The concentration of soluble CD95/Fas and of tumour necrosis factor-alpha receptor type 1 (sTNFR1) in the sera was quantified by ELISA. Activation-induced programmed T cell death was triggered by anti-CD3/CD28 antibodies and measured by 7-AAD staining. All immunological tests were performed at least 1 month after dialysis initiation. T cell proliferation in response to phytohaemagglutinin or anti-CD3 monoclonal antibodies was moderately diminished in non-dialysed patients and markedly reduced in haemodialysis patients compared to healthy controls (P < 0.01 and P < 0.001, respectively). In a mixed lymphocyte culture the proliferative response of T cells from dialysed patients was significantly diminished (P < 0.001). T cells of both non-dialysed and dialysed patients have augmented CD95/Fas and CD45RO expression, increased sCD95/Fas and sTNFR1 release and spontaneously undergo apoptosis. Culture of T cells from haemodialysis patients with anti-CD3/CD28 antibodies increased the proportion of CD4(+) T cells committing activation-induced cell death by a mean 7.5-fold compared to T-helper cells from non-dialysed patients (P < 0.001). Renal failure and initiation of haemodialysis results in a reduced proliferative T cell response, an aberrant state of T cell activation and heightened susceptibility of CD4(+) T cells to activation-induced cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / biosynthesis*
  • Apoptosis*
  • Cell Division
  • Female
  • Humans
  • Immunophenotyping
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / therapy
  • Leukocyte Common Antigens / biosynthesis
  • Male
  • Middle Aged
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Receptors, Tumor Necrosis Factor, Type I
  • Renal Dialysis*
  • Solubility
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • fas Receptor / biosynthesis*

Substances

  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • fas Receptor
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1