Herpesvirus ateles (HVA) and Herpesvirus saimiri (HVS) have been found to transform marmoset monkey-T lymphocytes leading to permanently established lymphoid cell lines. We have demonstrated that continuously growing HVA/HVS-transformed T-cell lines have the capacity to kill certain tumor-derived target cells in a short-term ?51?Cr release assay in vitro. Progress to date indicates that HVA/HVS-transformed cytotoxic cell lines correspond to marmoset natural killer (NK) cells and that their activity is subject to the same regulatory mechanisms as that of marmoset NK cells. The present investigation aims at further characterization of HVA/HVS cell line-mediated cytotoxicity and determination of whether this reactivity may be used as a general model system to study lymphocytotoxic mechanisms. The questions to be approached include: Is the lytic mechanism and its regulation displayed by HVA/HVS cell lines representative of that (or those) used by normal cells? Do effector cell receptors and target antigens reflect naturally occurring receptors or antigens? Can transformed cell lines be established that express other cell-mediated immune functions as well as antigen specificity? Specifically, the cytotoxicity mechanism expressed by HVA/HVS-transformed cell lines are being characterized and compared to nontransformed effector cells with regard to target-cell specificity and influences of various inhibitors, mediators, and inducers. Attempts will be made to clone HVA/HVS cytotoxic cells and prepare monoclonal antibodies against effector-cell receptors involved in recognition and cytotoxicity. The production of cytolytic factor(s) from the """"""""NK-like"""""""" cell lines has been investigated and will be characterized biochemically. Other possible cell-mediated functions (helper or suppressor activity) will be determined, and the creation of antigen-specific functional cell lines will be investigated. These results will be used to ascertain the relevance of this system for the study of lymphocytotoxic mechanisms and its significance for cellular immune function. (LB)
