IMMUNE REGRESSION OF VISCERAL METASTASES IN ATHYMIC MICE

Abstract

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-H-2 histocompatibility antigens. This rejection corresponds directly with 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 demonstrated the effectiveness of adoptively transferred, sensitized BALB/c lymphocytes in eliminating preexisting visceral metastases in BALB/c athymic mice. 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. Graft rejection in vivo and cell-mediated cytotoxicity in vitro are mediated by T [thymus-derived] cells. Enriched sensitized B [bone marrow-derived] cells and anti-MDAY-D2 serum are incapable of mediating this graft rejection in vivo. 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.