Chronic inflammation and T cell zeta-chain downregulation in hemodialysis patients

Am J Nephrol. 2008;28(1):152-7. doi: 10.1159/000110020. Epub 2007 Oct 19.

Abstract

Background: Clinical and experimental data indicate a deficient immune response in hemodialysis (HD) patients. zeta-Chain phosphorylation is an early and central event in the process that follows antigen recognition by the T cell antigen receptor (TCR). T cell zeta-chain is downregulated in many chronic inflammatory states, such as cancer, autoimmune disease and chronic infection. HD is also characterized as a chronic inflammatory state. The aim of the present study was to evaluate T cell zeta-chain expression in HD patients.

Patients and methods: Thirty-three stable HD patients and 30 healthy volunteers were enrolled into the study. T cell count, the percentage of zeta-chain-positive T cells, as well as T cell zeta-chain mean fluorescence intensity (MFI) were evaluated with flow cytometry. The inflammatory markers C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were measured in the serum by means of ELISA.

Results: All the evaluated markers of inflammation were increased in HD patients. In these patients, T cell zeta-chain MFI was decreased. CD3-epsilon MFI did not differ between the two groups indicating that among the TCR complex constituents, zeta-chain is selectively downregulated.

Conclusions: HD is a state of chronic inflammation. Like in other pathological chronic inflammatory conditions, T cell zeta-chain is downregulated in HD patients. Since zeta-chain plays a key role in the transduction of the signal that follows antigen recognition by the TCR, its downregulation could be responsible for the deficient cellular immune response observed in HD patients.

MeSH terms

  • Aged
  • C-Reactive Protein / metabolism
  • CD3 Complex / metabolism
  • Chronic Disease
  • Down-Regulation / immunology
  • Female
  • Humans
  • Inflammation / immunology*
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / therapy
  • Lymphocyte Count
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism*
  • Renal Dialysis
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • CD3E protein, human
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • C-Reactive Protein