Innate immunity in transplant tolerance and rejection

Historically, research on transplant rejection and tolerance has focused on cells of the adaptive immune system, especially T cells. Anti-graft effector T cells are necessary and sufficient for the rejection of most allografts, while regulatory T cells, either arising naturally or as a result of a specific treatment regimen, are crucial to long-term graft tolerance. Although the role of T cells in transplant rejection and tolerance is well-established, the role that the innate immune system plays in these processes is only recently being appreciated. Cells of the innate immune system, such as dendritic cells (DCs) and natural killer cells, can become activated by microbial products or endogenous pro-inflammatory ligands released during the mechanical and ischemia-reperfusion injury associated with transplantation surgery, promoting the initiation of T-cell responses against the graft. In addition, innate immune cells are required for acute and chronic rejection in certain animal transplant models and by extension perhaps in clinical transplantation. However, innate immune cells are also implicated in the establishment of transplant tolerance through mechanisms including elimination or inhibition of activated host effector T cells and killing of donor DCs. A deeper understanding of the functions of the innate immune system during transplantation may lead to more successful tolerance strategies.