Role of regulatory T cells in xenotransplantation

Purpose of review Although much has been written about the biology of regulatory T cells (Tregs), their characterization and role in xenotransplantation has been limited. This review summarizes the recent literature supporting a role for Tregs in the cell-mediated xenoimmune response. Recent findings Studies in in-vitro assays systems have focused on the biology of natural Tregs, whereas in-vivo rodent models of induced tolerance to xenografts have implied an important role for CD4(-)CD8(-) double-negative T cells. Although it was not unexpected that natural Tregs would have the capacity to modulate the T-cell-mediated response to xenografts, there are features that are different to what is seen in alloimmunity. The Tregs response to pig xenografts is more dependent on immunomodulatory cytokines such as IL-10, whereas in-vitro Tregs function in alloimmunity is focused strongly on cell contact mechanisms. In the acquired immune response, the majority of published findings have highlighted the properties of CD4(-)CD8(-) double-negative Tregs, whereas little if anything has been written about the more familiar CD4(+)D25(+) Tregs, which has been well described with in-vivo models of acquired alloimmune tolerance. Summary Although many investigators feel there are unique opportunities for using cell-based immunomodulatory therapies in xenotransplantation, our current understanding of the biology of Treg response remains incomplete. These gaps in our understanding need to be overcome before Tregs can be realized therapeutically to modulate the strong cellular xenoimmune response.