Dominant regulation: a common mechanism of monoclonal antibody induced tolerance?

Transplantation tolerance can be induced by a range of agents that block T cell/antigen-presenting cell (APC) interactions known to be important for initiation of the adaptive immune response. Tolerance so induced has been shown to have a regulatory phenotype dependent on CD4+ cells. This was first observed with nonlytic anti-CD4 antibodies, and was recently demonstrated following other therapeutic approaches. Dominant tolerance also plays a role in natural regulation of the immune response, functioning to prevent autoaggressive cells mediating self-destruction. The mechanism by which dominant tolerance is established and maintained remains unclear, and the reported characteristics of regulatory cells in different experimental models vary widely. Here we review the evidence for potential mechanisms involved and propose that there is a common pathway by which dominant tolerance is mediated.