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

Transplantation
Emmanuel BoleslawskiY Calmus

Abstract

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. 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. 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...Continue Reading

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Citations

Aug 21, 2007·Molecular Diagnosis & Therapy·Mercè BrunetOlga Millán
Dec 12, 2012·Transplantation·Jason M ZimmererGinny L Bumgardner
Aug 5, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·O MillánM Brunet
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Aug 8, 2015·Clinical Biochemistry·Eberhard Wieland, Maria Shipkova
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