Abrogation of the in vitro generation of the cytotoxic T-cell response to a murine tumor: the role of suppressor cells.

Abstract

A reproducible in vitro assay for the effect of suppressor T cells on the generation of an in vitro cytotoxic response to a metastatic murine tumor is described. Suppression in this system is maximal. The model uses splenic T cells from DBA/2 mice bearing the MDAY-D2 metastatic tumor as suppressors of the in vitro generation of a cell mediated cytotoxic response by syngeneic tumor-bearer (i.e., primed) peripheral lymph node cells stimulated with mitomycin C-treated MDAY-D2 tumor cells. The effect of the cell mediated cytotoxic response is profound, specific and mediated by splenic T cells. The suppressor T cells appear to impair precursor rather than mature cytotoxic cells. A highly immunogenic variant of MDAY-D2, namely MDWI, does not generate a suppressor response. Suppressor T cells from an MDAY-D2 tumor-bearer cannot suppress the in vitro response to MDWI. This model of potent suppressor T-cell action is highly reproducible and offers an opportunity for the analysis of why some tumors generate an effective cell mediated cytotoxic response which others stimulate dramatic suppressor T-cell response.