Apoptotic cell-linked immunoregulation: implications for promoting immune tolerance in transplantation

The induction of alloantigen-specific immune tolerance is the Holy-Grail in transplantation. Although it had been previously demonstrated that transient depletion of T cells through apoptosis could lead to long-term immune tolerance, the underlying mechanism responsible for this tolerance induction and maintenance was unknown. In this short article, a novel mechanism for long-term immune tolerance via transient T cell apoptosis will be discussed, based on our recent findings in a CD3-specific antibody treatment-induced immune tolerance mouse model. Transforming growth factor-beta, which is produced by immature dendritic cells whilst they phagocytose apoptotic T cells and by macrophages, plays an important role in initiating long-term immune tolerance. A possible model of how allospecific-immune tolerance can be induced in order to prevent allograft rejection in transplantation will be also proposed.