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

BackgroundThe 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.MethodsCore 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.ResultsRecruitment 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 (0.3 ± 0.004/HPF) were significantly fewer in all biopsies after LTx compared to the control (0.7 ± 0.04/HPF).ConclusionsThese 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.

► We investigated the distribution of T, NK and NKT cells in transplanted livers.
► Cells were analyzed in liver core biopsies using immunofluorescence.
► NK cells were significantly lower in biopsies after LTx compared to the control.
► Recruitment of intrahepatic T cells revealed significant increase after LTx.
► CD3+CD56+NKT cell numbers decreased significantly during severe graft rejection.