Approaching tolerance in transplantation
Lin CY., Graca L., Cobbold S., Waldmann H.
The past 15 years have seen a substantial increase in our knowledge of how short-term therapy with a range of antibodies that block immune function can induce a state of immunological tolerance to transplants. The paradigm established with CD4 antibodies now seems equally applicable to many other tolerance inducing agents. It would seem that antibody therapy is required to create a complete ceasefire in the immune system's attack on the transplant. During this ceasfire donor antigen is processed by host antigen-presenting cells and made available in a form that allows selective expansion of specialised T-cells with regulatory function. Such T-cells police the immune system and stop attack directed to antigens physically associated with those from the transplanted tissue. Antigens from the transplanted tissue provide a constant impetus to keep regulatory T-cell activity dominant so that the system remains effectively policed. New cohorts of regulatory T-cells replenish effete cells over time through « infectious tolerance ». Knowledge of these dominant tolerance mechanisms may allow for optimisation of combined strategies for tolerance, and for evolution of tolerogenic vaccines in transplantation.