Regulatory cells in transplantation.

Regulatory T cells can play an important role in both the induction and maintenance of tolerance to donor alloantigens in vivo. Regulatory activity specific for donor alloantingens is enriched amongst CD4+CD25+ T cells in some settings and can be induced by manipulating the immune system before transplantation. Donor alloantigen-specific CD4+CD25+ regulatory T cells can control aggressive CD4+ as well as CD8+ T cells thereby preventing rejection and can mediate linked unresponsiveness. In vivo, donor alloantigen specific CD4+CD25+ cells are dependent on interleukin (IL)10 and CTLA4 for functional activity. These populations of regulatory cells induced by manipulating the adult immune system therefore have properties in common with naturally occurring regulatory T cells. The active regulation/suppression of immune responsiveness to donor alloantigens offers a way to silence aggressive immune responses directed to donor alloantigens thereby preventing damage to the graft from being inflicted. The generation of regulatory T cells with defined alloantigen specificity could provide dynamic control of rejection responses and offers a potential route to permanent graft survival without the need for life-long non-specific immunosuppression.