The presence of Foxp3 expressing T cells within grafts of tolerant human liver transplant recipients.
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<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.


CONCLUSIONS
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.
Li
Ying
Y
Innovation Center for Immunoregulation Technologies and Drugs, Transplant Tolerance Unit, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Zhao
Xiangdong
X
Cheng
Donghua
D
Haga
Hironori
H
Tsuruyama
Tatsuaki
T
Wood
Kathryn
K
Sakaguchi
Shimon
S
Tanaka
Koichi
K
Uemoto
Shinji
S
Koshiba
Takaaki
T
D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008107:Liver Diseases / Q000145:classification / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger