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Immune regression of visceral metastases in athymic mice. Correlation of "low-level" in vitro cell-mediated cytotoxic reactions with allograft rejection in vivo.

The MDAY-D2 tumor of DBA/2 origin metastasizes widely and predictably in syngeneic DBA/2 mice, as well as in allogeneic athymic mice. BALB/c mice, which are H-2 compatible with MDAY-D2, reject the tumor based on non-H2 histocompatibility antigens. This rejection corresponds directly with the generation of a "low-level," in vitro, cell-mediated cytotoxic response in ipsilateral peripheral lymph nodes and spleen. Production of cytotoxic antibody also occurs during tumor rejection. Previous work has demonstrated the effectiveness of adoptively transferred, sensitized BALB/c lymphocytes in eliminating preexisting visceral metastases in BALB/c athymic mice. The present study shows that in this model the complete regression of H-2-compatible allografts, in the form of preexisting metastases, correlates directly with the ability of adoptively transferred cells to mediate low-level, cell-mediated cytotoxicity in vitro. Both graft rejection in vivo and cell-mediated cytotoxicity in vitro are mediated by T cells. Enriched sensitized B cells and anti-MDAY-D2 serum are both incapable of mediating this graft rejection in vivo. Based on these findings, we conclude that relatively weak in vitro cell-mediated cytotoxic responses should not be dismissed as biologically insignificant, for they may be indicative of considerable immune potential in vivo.