The Presence of Foxp3 Expressing T Cells Within Grafts of Tolerant Human Liver Transplant Recipients

Abstract

Background. Some experimental transplant-tolerance models have shown that the presence of regulatory T cells within grafts is important for the development of tolerance (Tol). Methods. To determine if the presence of regulatory T cells correlates with graft acceptance in living-donor liver-transplantation tolerance, the expression of Foxp3 mRNA and the presence of CD4⁺, CD8⁺, and Foxp3⁺ cells were quantified in biopsies from tolerant recipients by real-time polymerase chain reaction and by immunohistochemistry and immunofluorescent staining (Gr-Tol). The results were compared with biopsies from the recipients on maintenance immunosuppression (Gr-IS), grafts removed because of chronic rejection (Gr-CR), or normal liver (Gr-NL). Results. The expression of Foxp3 mRNA in Gr-Tol was higher than that in Gr-IS (P=0.07) and Gr-NL (P+ cells were detectable within the clustered CD4⁺ and CD8⁺ cells in the portal areas. Ninety-two percent of those Foxp3⁺ cells were CD4⁺, whereas 8% were CD8⁺. The number of Foxp3⁺ cells was significantly increased in Gr-Tol, compared with that in Gr-IS (P+ or CD8⁺ cells did not differ between the two. Foxp3⁺ cells were hardly detectable in Gr-CR or -NL. Conclusions. This is the first report showing that CD4⁺Foxp3⁺ cells are present within grafts in a subset of tolerant patients after human liver transplantation. A prospective study is needed to elucidate whether the assessment of intragraft expression of Foxp3 protein, but not Foxp3 mRNA, can aid the identification of living-donor liver-transplantation recipients who can successfully withdraw IS.