In vivo generation of tumor-specific cytotoxic T-cells in the regional lymph node: effect of subcutaneous inoculation of mls-disparate spleen cells around implanted tumors in mice.

Generation of immunological resistance to a B-cell tumor was attempted by inoculating histoincompatible spleen cells around the sites of implanted tumor cells. Syngeneic hybridomas developed in the regional area of 96% of the control mice but in 4% of the mice that had received s.c. inoculation of H-2-matched, mls-disparate spleen cells. The regional lymph node cells of the mice in which tumors did not develop showed direct cytotoxicity against the hybridoma cells. This cytotoxicity was sensitive to treatment with the monoclonal anti-Thy-1.2 and complement and was specific for the tumor cells. After s.c. inoculation of mls-disparate spleen cells, cells of the regional lymph node were shown to produce interleukin 2. Primary cultures of the recipient lymph node cells and the donor spleen cells in the presence of T-cell growth factors showed that the tumor-specific cytotoxic T-lymphocytes were derived from the donor spleen cells. These results strongly suggest that on injection of mls antigen-disparate spleen cells, injected splenic T-cells specific for the tumor developed into functional cytotoxic T-lymphocytes with the help of interleukin 2 which was produced by the mixed lymphocyte reaction in vivo and thus prevented tumor growth. The possibility of clinical application of this procedure in the immunotherapy of neoplasms is discussed.