INSIGHT INTO THE MECHANISM OF TCR-V-BETA-8-CELL-MEDIATED MOPC-315 TUMOR-ERADICATION( CD8+ T)

We have previously shown that depletion of TCR-V beta 8+ T cells by tr eatment with mAb reduces the curative effectiveness of low dose melpha lan (L-phenylalanine mustard; L-PAM) for mice bearing a large MOPC-315 tumor and extensive metastases. Here we show that V beta 8(+)/CD8(+) T cell lines derived from mice that are in the process of immune-media ted eradication of a large MOPC-315 tumor as a consequence of low dose L-PAM therapy (L-PAM TuB mice) are capable of mediating tumor eradica tion in vivo upon adoptive transfer. Analysis of the possible mechanis ms through which these cell lines bring about tumor eradication reveal ed that the V beta 8(+)/CD8(+) cells can exert in vitro a potent lytic activity and secrete large amounts of IFN-gamma. Both of these activi ties can be triggered by the MOPC-315 but not the MOPC-104E plasmacyto ma and are restricted by the MHC class I H-2K(d) molecule. in vivo neu tralization of IFN-gamma by treatment with mAb was found to cause a no ticeable delay in tumor rejection in mice subjected to adoptive chemoi mmunotherapy with low dose L-PAM and V beta 8(+)/CD8(+) cells; however , all tumors did regress after initial growth. Thus, the V beta 8(+)/C D8(+) cells use an IFN-gamma-dependent mechanism for the realization o f their in vivo tumor-eradicating immunity. However, an IFN-gamma-inde pendent mechanism, most likely involving direct V beta 8(+)/CD8(+) CTL activity, is apparently also used.