Induction of Regulatory T-cells by Donor-Specific Blood Transfusion in the Absence or Presence of Liver Allograft Transplantation (141.43)

Abstract

Abstract Donor-specific blood transfusion (DST) has been shown to be effective at inducing tolerance and long-term survival in animals transplanted with MHC-mismatched tissue. The objective of this study was to ascertain how DST alone or in combination with liver allograft transplantation (LTx) affects the generation and function of regulatory T-cells in vitro and in vivo. We found that DST alone generates CD4+ T-cells that when transferred into naïve recipients suppress liver allograft rejection despite expressing little or no Foxp3 at the time of adoptive transfer. In addition, we present the novel finding that DST plus LTx (but not DST alone) increases the formation of Foxp3-expressing regulatory T-cells (Tregs) that suppress alloantigen-induced activation in vitro as well as induce long term tolerance to liver allografts when adoptively transferred into naïve recipients prior to LTx. Finally we demonstrate that virtually all Foxp3-expressing Tregs reside within the CD4+CD45RC- population whereas these Tregs are equally distributed between the CD4+CD25+ and CD4+CD25- populations. Taken together, our data suggest that DST administration, in the absence of allograft transplantation, induces the formation of CD4+ T-cells that are not Tregs themselves but develop into fully functional Foxp3+ Tregs or help to induce the formation of Foxp3+ Tregs following allograft transplantation.