Immunoregulatory Role Of Donor Liver Natural Killer (NK) Cells In Allogeneic Organ Transplant-Ation

Objective:To investigate the machenism of donor liver NK cells alleviating actuerejection after liver transplantation by observing the secretion level of TGF-β1andIFN-γ in peripheral blood and the protein expression of Arg-1and iNOS in livertissues in acute liver graft rejection rat modelsMethods:Lewis rats were used as liver graft donors and BN rats asrecipients,“Lewis-BN” as acute rejection model was established by the modifiedtwo-cuff method.The donor leukocytes were depleted by total body irradiation of Co⁶⁰source, and the donor passenger leukocyte immunity were reconstituted bytransfusion donor liver NK cells via portal vein during the course of transplantation ofthe irradiate liver. Three various transplantation groups were designed: Group A.acute rejection group（Lewis-BN）, Group B. Co⁶⁰irradiation acute rejectiongroup(Co⁶⁰-Lewis-BN), C. Co⁶⁰irradiation+donor liver NK cells transfusion viaportal vein acute rejection group (Co⁶⁰-Lewis-BN+donor NK cells).The recipientswere sacrificed day1,day3,day7posttransplantation respectively, TGF-β1and IFN-γlevel in peripheral blood, Arg-1and iNOS protein expression in liver tissues andhistopathological of liver grafts were observed and detected. The survival quality andliving time in crude survival subgroup were observed. Results: Statistical difference of acute rejection and average survival time among thethree groups was found:on day7posttransplantation,acute rejection in B group wasmore severe than A group（RAI：8.50±0.22vs.6.0±0.36, P＜0.05）.The averagesurvival time in B group was also significantly shorter than A group（13.75±1.532dvs.45±3.396d，P＜0.05）; On day7posttransplantaiton,acute rejection in C groupwas less severe than B group（RAI：7.33±0.21vs.8.50±0.22, P＜0.05）.Theaverage survival time in C group was also significantly longer than B group（26±5.092d vs.13.75±1.532d，P＜0.05）.These suggest that donor liver NK cellstransfution via portal vein can alleviate the actue rejection and prolong the averagesurvival time of the recipients.On day7posttransplantation, peripheral blood TGF-β1levels in group B weresignificantly lower than group A and group C（11.0±0.57vs.28.0±6.08ng/ml，11.0±0.57vs.27.6±1.45ng/ml，P＜0.01）, but peripheral blood IFN-γ levels in group Bwere significantly higher than group A and group C（383.21±9.82vs.112.76±4.24pg/ml,383.21±9.82vs.213.52±5.78pg/ml,P＜0.01）.These suggest that donorliver NK cells transfution via portal vein can alleviate the actue rejection by elevatingTGF-β1levels and decreasing IFN-γ levels in peripheral blood.On day7posttransplantation,Arg-1expression of the liver in group B weresignificantly lower than A group（Arg-1/actine:0.687±0.04vs.0.487±0.03, P＜0.05）, iNOS expression of the liver in group B were significantly higher than Agroup （iNOS/actine:0.05±0.01vs.0.23±0.03, P＜0.05）; On day7posttransplantation,Arg-1expression of the liver in group C were higher than B group（Arg-1/actine:0.487±0.03vs.0.605±0.08，P＜0.05）, iNOS expression of the liverin group C were lower than B group（iNOS/actine:0.23±0.03vs.0.09±0.02，P＜0.05）;These suggest that donor liver NK cells transfution via portal vein canalleviate the actue rejection by increasing the Arg-1expression and declining theiNOS expression in liver grafts.Conclusion:1. Donor liver NK cells can alleviate liver allograft acute rejection and polarize the Th1/Th2cytokins paradigm to Th2cytokins in peripheral blood,which revealed thatthe expression of TGF-β1and IFN-γ in peripheral blood may be used as anmonitoring indicator for acute rejection.2. Regulation of recipient T cells immune function by donor liver NK cells may beassociated with the up-regulated expression of Arg-1and down-regulated expressionof iNOS via effects on the L-arginie metabolism.