The immune system’s cytotoxic response to foreign antigens is important in relation to defence against harmful pathogens. However, in the context of skin transplantation, immune activation culminates ultimately in graft rejection. Immune suppression can be prescribed to prolong graft survival, but at the expense of generalised immune deficiency and organotoxicity. Another avenue to prolong skin graft survival is through upregulation of regulatory T cells (Treg), the body’s natural tolerance cells. This can be achieved through the activity of the intracellular enzyme indoleamine 2,3dioxygenase (IDO); The IDO generated microenvironment is supportive of Treg cell proliferation and survival but toxic to CD8+ and CD4+CD25- T cells. Treg cells recognise and are activated by specific antigens presented to them on MCH II by antigen presenting cells. Fibroblasts are non-professional antigen presenting cells that express MCH class II. Although not ubiquitously expressed, they can be induced to express IDO on stimulation with interferon-gamma (IFN-γ). We hypothesize that Treg cells upregulated through an allogeneic fibroblast-IFN-γ co-culture may induce tolerance to specific allo-antigens. Local delivery of this upregulated Treg population in vivo via a matrix delivery system may preferentially confer tolerance to a specific skin allograft.