Publisher Summary This chapter discusses earlier experience in preventing the formation of the ternary complex and discusses some newer attempts to induce unresponsiveness in experimental animals. The three components of the complex serve as independent targets for development of strategies aimed at disrupting the trimolecular complex. The earliest attempts at immunotherapy targeting the T cell used anti-lymphocyte serum and monoclonal antibodies directed at the Thy-1 antigen, a marker for all T cells, to eliminate or downregulate T cell activation. The development of hybridoma technology made available reagents, which could target a specific cell population. The chapter discusses the use of antibodies directed at various proteins on the T cell surface in regulating T cell responses, examines T cells as effectors of immune regulation. This approach involves the use of antigen-specific T cell lines or clones as vaccinating agents to elicit “anti-idiotypic” regulator T cells capable of inhibiting the response of the antigen-specific T cell population. As opposed to passive administration of antibodies, this approach involves active participation of the individual's immune system in inducing a regulatory response to the immunizing cells. Among the potential immunotherapeutic strategies outlined in this chapter the most favored is the therapy that is most selective in turning off autoantigen-specific T cells while sparing the rest of the immune response.