Abstract
The aim of this study is to compare the histological grading of acute organ rejection according to the Banff score with intracellular interleukin-2 (IL-2) concentrations in cytotoxic CD8+ T cells from peripheral blood samples. 66 recipients after liver transplantation and 20 healthy controls were included into this study. Blood samples of liver transplant recipients were collected beside routine visits or, in case of suspected organ rejection, with additional liver biopsy. For cytometry, the blood cells were stained with CD3, CD8 and intracellular-IL-2. The percentage of cells with detectable intracellular IL-2 was significantly increased in patients with acute rejection (n = 7, P < 0.001, t Test) compared to recipients without rejection. The percentage of cells with detectable intracellular IL-2 (mean ± SEM) was 7.6 ± 0.9% in rejection patients, 2.3 ± 0.22% in stable liver transplant recipients, and 14 ± 2.99% in healthy controls. Intracellular IL-2 correlates to the Banff score in rejection patients (Spearmans-rho = 0.81, P < 0.05). This cytometric method shows a good sensitivity (71%) with a cut-off based on a high specificity of 95% for histological proven organ rejection in our study cohort. Measurement of intracellular IL-2 in cytotoxic CD8+ T-lymphocytes by flow cytometry correlates very well to the histological grading according to the Banff score and shows a good sensitivity and excellent specificity in acute organ rejection.
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Conti F, Dousset B, Archambeau D, Louvel A, Houssin D, Calmus Y (1995) Enhanced risk of steroid-resistant acute rejection following pretransplant steroid therapy in liver graft recipients. Transplantation 60:1104–1108
Hirose R, Roberts JP, Quan D et al (2000) Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation. Transplantation 69:307–311
Andreu H, Rimola A, Bruguera M et al (2002) Acute cellular rejection in liver transplant recipients under cyclosporine immunosuppression: predictive factors of response to antirejection therapy. Transplantation 73:1936–1943
Hojo M, Morimoto T, Maluccio M et al (1999) Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397:530–534
van Twuyver E, de Hoop J, ten Berge RJ et al (1996) Comparison of T cell responses in patients with a long-term surviving renal allograft versus a long-term surviving liver allograft it’s a different world. Transplantation 61:1392–1397
Koch M, Niemeyer G, Patel I, Light S, Nashan B (2002) Pharmacokinetics, pharmacodynamics, and immunodynamics of daclizumab in a two-dose regimen in liver transplantation. Transplantation 73:1640–1646
Niemeyer G, Koch M, Light S, Kuse ER, Nashan B (2002) Long-term safety, tolerability and efficacy of daclizumab (Zenapax) in a two-dose regimen in liver transplant recipients. Am J Transplant 2:454–460
Nikaido T, Shimizu A, Ishida N et al (1984) Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature 311:631–635
Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL (1991) Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807–815
Ho S, Clipstone N, Timmermann L et al (1996) The mechanism of action of cyclosporin A and FK506. Clin Immunol Immunopathol 80:S40–S45
Batiuk TD, Pazderka F, Halloran PF (1995) Calcineurin activity is only partially inhibited in leukocytes of cyclosporine-treated patients. Transplantation 59:1400–1404
Platz KP, Mueller AR, Rossaint R et al (1996) Cytokine pattern during rejection and infection after liver transplantation-improvements in postoperative monitoring? Transplantation 62:50–1441
Banff schema for grading liver allograft rejection: An international consensus document (1997) Hepatology 25:658–663
O’Grady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A (2002) Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet 360:1119–1125
Boleslawski E, Conti F, Sanquer S et al (2004) Defective inhibition of peripheral CD8+ T cell IL-2 production by anti-calcineurin drugs during acute liver allograft rejection. Transplantation 77:1815–1820
Veronese FV, Manfro RC, Roman FR et al (2005) Reproducibility of the Banff classification in subclinical kidney transplant rejection. Clin Transplant 19:518–521
Nankivell BJ, Chapman JR (2006) The significance of subclinical rejection and the value of protocol biopsies. Am J Transplant 6:2006–2012
Dallman MJ, Shiho O, Page TH, Wood KJ, Morris PJ (1991) Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway. J Exp Med 173:79–87
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Funding: Harry and Peter Fuld-Foundation, Germany.
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Akoglu, B., Kriener, S., Martens, S. et al. Interleukin-2 in CD8+ T cells correlates with Banff score during organ rejection in liver transplant recipients. Clin Exp Med 9, 259–262 (2009). https://doi.org/10.1007/s10238-009-0042-4
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DOI: https://doi.org/10.1007/s10238-009-0042-4