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

Innovation Center for Immunoregulation Technologies and Drugs, Transplant Tolerance Unit, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Transplantation (Impact Factor: 3.83). 12/2008; 86(12):1837-43. DOI: 10.1097/TP.0b013e31818febc4
Source: PubMed


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).
The expression of Foxp3 mRNA in Gr-Tol was higher than that in Gr-IS (P=0.07) and Gr-NL (P<0.0001), but equivalent to that in Gr-CR. In Gr-Tol, Foxp3 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<0.05), although the number of CD4 or CD8 cells did not differ between the two. Foxp3 cells were hardly detectable in Gr-CR or -NL.
This is the first report showing that CD4Foxp3 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.

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Available from: Tatsuaki Tsuruyama
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    • "). Li et al. have further confirmed that higher percentages of FoxP3 + cells are also detected in biopsy material from some tolerant liver transplant patients (Li et al., 2008). More recently, expansion of in vivo numbers of circulating Tregs has been strongly linked to immunosuppression withdrawal protocols and establishment of tolerance in cohorts of liver transplant recipients (Nafady-Hego et al., 2010). "
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