We described a series of experiments which focus on the mechanisms of immunosuppression of T cell mediated contact sensivity responses. Our working hypothesis assumes that there are at least three distinct suppressor T cells in the suppressor cell cascade. The signals responsible for the induction of these suppression T cells (Ts) will be explored using genetic and immunological approaches. Furthermore, we will evaluate the mechanisms responsible for the I-J restrictions characteristic of some of these Ts subsets. Once the Ts are generated, some subsets (e.g., Ts3) require an additional specific activation signal. We propose to characterize the process of T cell activation using conventional immunological procedures and by using a series of inducible pre-Ts3 hybridomas. These inducible hybridomas only secrete Ts3 derived suppressor factor (TsF3) which mediates the biological activity of the Ts3 cells after specific activation with TsF2. The creation and analysis of a series of double hybridomas may reveal a molecular basis for TsF2 and TsF3 specificity and genetic restrictions. Finally, the terminal stages of the suppressor cell cascade are poorly defined. We propose experiments to further dissect this portion of the suppressor pathway. Since immunosuppression is a regulatory process, it is important for the homeostasis of the immune system. Aberrations in the suppressor cell pathway have been implicated in several human diseases. In addition to its general biomedical importance, our proposed studies will be directly applied to one experimental disease model -- schistoso iasis.
