Distribution of intrahepatic T, NK and CD3(+)CD56(+)NKT cells alters after liver transplantation: Shift from innate to adaptive immunity?

Werner, Jens M. and Lang, Corinna and Scherer, Marcus N. and Farkas, Stefan A. and Geissler, Edward K. and Schlitt, Hans J. and Hornung, Matthias (2011) Distribution of intrahepatic T, NK and CD3(+)CD56(+)NKT cells alters after liver transplantation: Shift from innate to adaptive immunity? TRANSPLANT IMMUNOLOGY, 25 (1). pp. 27-33. ISSN 0966-3274,

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Abstract

Background: The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances. Methods: Core biopsies of transplanted livers were stained with antibodies against CD3 and CD56. Several cell populations including T (CD3(+)CD56(-)), NK (CD3(-)CD56(+)) and NKT cells (CD3(+)CD56(+)) were studied by fluorescence microscopy. Cell numbers were analyzed in relation to the time interval after LTx, immunosuppressive therapy and stage of acute graft rejection (measured with the rejection activity index: RAI) compared to tumor free liver tissue from patients after liver resection due to metastatic disease as control. Results: Recruitment of CD3(+)CD56(+)NKT cells revealed a significant decrease during high RAI scores in comparison to low and middle RAI scores (RAI 7-9: 0.03 +/- 0.01/HPF vs. RAI 4-6: 0.1 +/- 0.005/HPF). CD3(+)CD56(+)NKT cells were also lower during immunosuppressive therapy with tacrolimus (0.03 +/- 0.01/HPF) than with cyclosporine (0.1 +/- 0.003/HPF), cyclosporine/MMF (0.1 +/- 0.003/HPF) or sirolimus (0.1 +/- 0.01/HPF) treatment Intrahepatic T cell numbers increased significantly 50 days after LTx compared to control liver tissue (4.5 +/- 0.2/HPF vs. 1.9 +/- 0.1/HPF). In contrast, NK cells (03 +/- 0.004/HPF) were significantly fewer in all biopsies after LTx compared to the control (0.7 +/- 0.04/HPF). Conclusions: These data indicate significant alterations in the hepatic recruitment of T, NK and CD3(+)CD56(+)NKT cells after LTx. The increase in T cells and the decrease in NK and CD3(+)CD56(+)NKT cells suggest a shift from innate to adaptive hepatic immunity in the liver graft. (C) 2011 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: NATURAL-KILLER-CELLS; LYMPHOCYTE RECRUITMENT; ALLOGRAFT-REJECTION; TOLERANCE; PATHWAYS; TACROLIMUS; INDUCTION; SURVIVAL; INJURY; ORGAN; Liver transplantation; Intrahepatic lymphocyte recruitment; Immune regulation; CD3(+)CD56(+)NKT cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Jun 2020 10:26
Last Modified: 08 Jun 2020 10:26
URI: https://pred.uni-regensburg.de/id/eprint/20577

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