T-T Cell Synergy in the in Vitro Generation of Secondary Cell-Mediated Cytotoxicity Against Syngeneic SV-40 Transformed Cells

Abstract

Abstract The concept of T-T cell interaction that was first suggested during cell-mediated immune response to alloantigens was evaluated in vitro in a syngeneic tumor system. Combinations of lymph node and thymus cells from mice immune against SV-40 transformed cells were shown to exhibit synergism with respect to in vitro generation of secondary cytotoxic effector cells against the corresponding target cells. That is, the activity exhibited by combinations of lymph node and thymus cells was greater than that given by equal numbers of the two cell types cultured separately. With respect to the kinetics and magnitude of effector cell generation, the response occurring in synergizing cultures closely resembled that of optimal numbers of lymph node cells. In addition, the antigen specificity of effector cells generated by synergizing cultures was similar to that of effectors derived from cultures containing optimal numbers of responding lymph node cells. Pretreatment of either lymph node or thymus cells with mitomycin C or x-ray irradiation completely abolished their synergistic interaction. The lymph node and thymus cell populations participating in synergy were found to be thymus dependent. since we have previously shown that similar T-T cell interaction occurs in rejection of a syngeneic SV-40 induced sarcoma in mice, it is proposed that the in vitro generation of secondary cytotoxicity provides an in vitro model for the study of in vivo thymus cell interactions in response to tumor-associated antigens. These results suggest that we may be dealing with the same or similar T cell populations described before as displaying synergy in response to alloantigens in the graft-vs-host, mixed lymphocyte, and cell-mediated cytotoxicity reactions.