Tolerance can be induced in the adult immune system

The immune system uses diverse mechanisms of self-regulation to enable it to respond to dangerous pathogens whilst avoiding damage to “self”. Amongst these, regulatory T-cells are prime players. These cells can be harnessed therapeutically by giving them, numerical and functional advantages over T-cells that mediate damaging immunity. I will give examples using antibody-based co-receptor and co-stimulation blockade, and also by lymphocyte depletion with antibodies such as CAMPATH-1H, when depletion is followed by “Physician-Guided Reconstitution of the Immune System” (PARIS). Therapeutic antibodies can themselves be immunogenic, and lessons about mechanisms underlying immunogenicity, have been learned from strategies used to induce tolerance to the CAMPATH-1H antibody. These will be discussed briefly.