Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance

Although some previous studies have indicated the possibility of immunosupp ression withdrawal in clinical liver transpiantation, the mechanism of graf t acceptance is not clear. The aim of this study is to elucidate the allore activity against the donor and intragraft cytokine profiles in living donor liver transplant (LDLT) recipients with graft acceptance. In October 1999, we had 23 patients who survived without immunosuppression after LDLT with a median drug-free period of 25 months (range: 3-69 months). They consisted of six patients who were electively weaned by an elective weaning protocol and 17 either forcibly or accidentally weaned patients due to various caus es but mainly due to infection. We evaluated the alloreactivity against the donor in these patients by a mixed lymphocyte re action and intragraft cyt okine profiles by real-time rivers e transcriptase-polymerase chain reactio n. The development of donor-specific hyporcactivity was observed in the pat ients with graft acceptance. The cytokine pattern in the supernatant of the culture medium revealed a down regulation of T helper (Th) 1 cytokine INF gamma against the donor while no significant difference was seen in Th2 cyt okine IL-10. Regarding the intragraft cytokine profiles, we could find no a mplification of Th1 cytokines (IL-2, INF gamma) and IL4 while some of the p atients revealed a gene expression of IL-10 with no significant difference from that of the normal, untransplanted liver specimen. In addition, no dif ference was observed in any other cytokines (IL-1 beta, IL-8, IL-15, TNF al pha) compared with those of the normal controls. We propose that the down r egulation of Th1 cytokine is one possible mechanism of graft acceptance in LDLT recipients. (C) 2001 Elsevier Science B.V. All rights reserved.