FUNCTIONAL STUDIES OF TRANSFORMED NATURAL KILLER CELLS

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)