Defective inhibition of peripheral CD8+ T cell IL-2 production by anti-calcineurin drugs during acute liver allograft rejection

Transplantation. 2004 Jun 27;77(12):1815-20. doi: 10.1097/01.tp.0000129914.75547.b3.

Abstract

Background: The aim of this study was to evaluate calcineurin activity and interleukin-2 (IL-2) expression by peripheral blood cells as a means of assessing the immune status of liver transplant recipients.

Methods: Twenty-one patients were studied in a randomized study comparing cyclosporine and tacrolimus as the main immunosuppressive drug. Calcineurin activity was determined after separation of phosphorylated and dephosphorylated products of a calcineurin specific peptide substrate by high performance liquid chromatography(HPLC). Intracellular IL-2 expression was measured by flow cytometry. In 34 additional patients, intracellular IL-2 expression was prospectively measured.

Results: Calcineurin activity fell after transplantation. Values were marginally higher in patients with acute rejection (P=0.059). The percentage of IL-2-producing T cells fell after transplantation. This percentage did not differ between patients with and without rejection. In contrast, the proportion of IL-2-producing CD8+ T cells was higher in patients with acute rejection than in patients free of acute rejection (P=0.003). Moreover, pretransplantation IL-2 expression by CD8+ T cells was higher in patients who subsequently developed acute rejection, suggesting that IL-2 production may be constitutively higher in those patients. The results obtained in the 34 additional patients confirmed these results.

Conclusions: These data suggest that quantification of intracellular IL-2 in CD8+ T cells may be a useful index of immune status in liver transplant recipients. Preoperative IL-2 levels might serve to individually tailor the immunosuppressive regimen.

Publication types

  • Clinical Trial
  • Meta-Analysis
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Calcineurin Inhibitors*
  • Cyclosporine / therapeutic use*
  • Female
  • Follow-Up Studies
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-2 / biosynthesis*
  • Liver Transplantation / immunology*
  • Liver Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Reoperation / statistics & numerical data
  • Tacrolimus / therapeutic use*
  • Time Factors

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Interleukin-2
  • Cyclosporine
  • Prednisolone
  • Tacrolimus