An overview on non-T cell pathways in transplant rejection and tolerance

Purpose of Review: Recent studies have demonstrated unexpected roles for non-T cells, especially innate immune cells, in the regulation of transplant outcomes. In this review, we highlight our recent understanding on the role of natural killer cells, dendritic cells, and macrophages in the allograft response, and discuss whether such cells can be targeted for the induction of transplant tolerance. Recent Findings: There are unexpected roles for non-T cells in regulating transplant outcomes, and depending on the models and tolerizing protocols, the innate immune cells contribute significantly to both graft rejection and graft acceptance. Some innate immune cells are potent inflammatory cells directly mediating graft injury, while others regulate effector programs of alloreactive T cells and ultimately determine whether the graft is rejected or accepted. Furthermore, when properly activated, some innate immune cells promote the induction of Foxp3 Tregs whereas others efficiently kill them, thereby differentially affecting the induction of tolerance. These new findings unravel unexpected complexities of non-T cells in transplant models and may have important clinical implications. Summary: The innate immune cells contribute to both graft rejection and graft acceptance. Thus, a detailed understanding of the exact mechanisms and pathways that govern such opposing effects in transplant models may lead to the design of new tolerance protocols.