| Summary: | Cadaver skin grafts are commonly utilised as dermal replacement treatments for large burn injuries when an autologous donor tissue shortage exists. The limitation of this therapy is immune rejection. The adverse side effects of immune suppressive drugs make them unsuitable for this subset of individuals with large surface area burns, who are often clinically unstable. Thus, a gap in treatment exists to prolong survival of these skin grafts. The goal of this Masters research was to address this gap and induce tolerance to specific skin antigens in vitro. We hypothesized that we could expand a specific population of Treg in an allogeneic indoleamine 2,3-dioxygenase (IDO) fibroblast co-culture, on the basis of specific MHC class II expression by the fibroblasts and that the IDO generated micro-environment afford selective survival of regulatory T cells (Treg) over effector T cells.
Three specific aims were accomplished in this study. (1)We first showed that Treg could be expanded in an allogeneic IDO expressing fibroblast co-culture. (2) As a side project to this, we showed that naïve CD4 T cells could be converted to Treg in the same co-culture conditions. (3) In the next phase, the suppressive potential of the expanded and converted Treg populations were confirmed in a CD8 T cell suppression assay. We found that the Treg isolated from the allogeneic IDO expressing fibroblast co-culture, specifically suppressed CD8 proliferation to the allogeneic fibroblast antigens but not third party antigens. In contrast, the Treg from the control group did not suppress CD8 proliferation.
The findings presented in this thesis collectively prove expansion of an antigen specific Treg population and conversion of naïve CD4 T cells to antigen specific Treg, in an allogeneic IDO expressing fibroblast co-culture, in vitro. === Medicine, Faculty of === Medicine, Department of === Experimental Medicine, Division of === Graduate
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