Antigen-induced programmed T cell death as a new approach to immune therapy.

We describe recent advances in understanding a mechanism of peripheral tolerance that operates through antigen-induced programmed cell death of mature T lymphocytes. A three-phase model of this process, termed propriocidal regulation, involves: (i) activation of T cells to express growth lymphokines and their receptors, (ii) lymphokine-stimulated cell-cycle progression, and (iii) T cell receptor reengagement leading to programmed cell death. Based on this model, antigen was used to treat experimental allergic encephalomyelitis and caused profound deletion of autoreactive, encephalitogenic T cells as well as dramatic clinical and pathological improvement of the disease. The potential strengths and weaknesses of this approach to the clinical treatment of T-cell-mediated diseases are discussed.