Defective inhibition of peripheral CD8+ T cell IL-2 production by anti-calcineurin drugs during acute liver allograft rejection.
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.
Boleslawski
Emmanuel
E
Cellular Biology Laboratory, Department of Medicine, University of Paris V, Paris, France.
Conti
Filomena
F
Sanquer
Sylvia
S
Podevin
Philippe
P
Chouzenoux
Sandrine
S
Batteux
Frédéric
F
Houssin
Didier
D
Weill
Bernard
B
Calmus
Yvon
Y
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis*; D016031:Liver Transplantation / Q000276:immunology* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D012086:Reoperation / Q000706:statistics & numerical data; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine; D011239:Prednisolone; D016559:Tacrolimus