The objective of this project is to gain an understanding of the interaction of transformed cells with the host immune system. In response to a tumor, the immune system mobilizes mechanisms which, paradoxically, turn-off not only the specific anti-tumor resistance but the general immunological reactivity. Although many factors interact in the subversion of immune system, a key role belongs to active suppressor cell (SC). We will study the significance of host SC, with emphasis on T suppressor cells (TS) in three mouse tumor models: P815 mastocytoma, B16 melanoma and virus-induced lymphoma. All three are progressively growing tumors, antigenic for the syngeneic host. Our first aim is to study the development of TH and TS in the course of interaction of tumor cells with normal purified lymphocytes, under controlled conditions, both in vitro and in simulated in vivo conditions (implanted diffusible chambers and adoptive cell transfer). The role of specific tumor antigen and other tumor-derived factors will be studied. Indirect pathways leading to hyperactivity of TH and TS (and other SC) will be studied, namely, the triggering of inter-feron production in B cells and null cells by glycoproteins tumor cell membrane. The specificity of the tumor-activated immunoregulatory cells will be studied, in regard to their idiotypic and paratopic repertoire. Attempts will be made to intervene with the immunosuppressive cell reactions using exogenous lymphokines and specific anti-idiotypic probes.