Pons JA, Revilla-Nuin B, Baroja-Mazo A, Ramirez P, Martinez-Alarcon L, Sanchez-Bueno F, Robles R, Rios A, Aparicio P, Parrilla P
BACKGROUND: Human liver allografts do sometimes survive in a recipient after withdrawal of immunosuppression (IS), commonly referred to as "operational tolerance." Preliminary clinical data have suggested an increase in the frequency of regulatory T cells (Treg) CD4+CD25 high and FoxP3 expression in operationally tolerant liver transplant recipients (Gr-T). In the context of human liver transplantation, the dynamics of Treg have not been studied. We designed a prospective study to ascertain the profile of the Treg population and FoxP3 expression during IS withdrawal. METHODS: To identify such parameters, we analyzed peripheral blood mononuclear cell populations and FoxP3 mRNA expression in 12 liver allograft recipients under cyclosporine A-based IS, who showed stable function of the allograft for more than 2 years. RESULTS: An increase was observed in the frequency of CD4+CD25 high cells when the IS was withdrawn in Gr-T patients (n=5). These patients exhibited a 3.5-fold increase for relative mRNA FoxP3 expression before the complete IS withdrawal and this continued when IS therapy was stopped. In patients who suffered rejection (n=7) there was no increase in the CD4+CD25 high cells or FoxP3 expression. CONCLUSIONS: With the present study, the first evidence is provided that the increase of CD4+CD25 high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.
27/11/2008
19034005
Transplantation (
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