Analysis of the involvement of cells from donor and recipient mice in adoptive transfer of antitumor immunity.

In this study, we attempted to analyze the effector cells for adoptive transfer of protective immunity directed against a P815Ys tumor. The spleen, lymph node, and peritoneal exudate cells obtained from immune mice at Day 7 to Day 10 after last challenge were tested for their in vitro cell-mediated cytotoxicity against P815Ys cells, using a 4-hr 51Cr release assay. The immune spleen lymphocytes (ISL) showed no cytotoxicity, whereas the peritoneal exudate cells exhibited marked cytotoxicity. Unexpectedly, when ISL or peritoneal exudate cells were adoptively transferred i.v. into mice bearing the P815Ys tumor, it was the ISL but not the peritoneal exudate cells that provided the hosts with significant protection. Using alloantibodies for negative depletion of cells in ISL, it was found that, after treatments with anti-Thy 1.2 or anti-Lyt 1 antiserum plus complement but not with anti-Lyt 2 or complement alone, the protective capacity of ISL can be abolished, indicating that the effector cells for conferring protective immunity to the host are Lyt 1-bearing T-cells. Moreover, culture supernatants of ISL with or without mitomycin C-treated P815Ys contain helper factor, interferon, and interleukin 2, which enhanced the in vitro generation of cell-mediated cytotoxicity against P815Ys. Taken together, these results strongly suggest that the donor helper T-cells are the effector cells responsible for adoptive transfer of protective immunity. We next examined the contribution of host cells. Syngeneic mice were made to become either T-cell (with thymectomy and irradiation)- or macrophage (with the administration of silica) depleted and were then subjected to adoptive transfer experiments. Both the thymectomized and the silica-treated mice, after receiving the ISL, showed significantly better survival times than did normal mice. Thus, the data suggest that the elimination of T-cells or inactivation of macrophages, presumably with immunosuppressive activity in the recipients, will allow further improvement of their battle for survival against tumor.