Suppression of tumor rejection by autologous anti-idiotypic immunity.

Autologous anti-idiotypic responses to tumorspecific lymphocytes altered the capability of mice to reject syngeneic tumors. This was shown by using two non-crossreacting fibrosarcoma lines, 1591 and 1316, induced by ultraviolet light. Cells from these tumor lines are regularly rejected when transplanted into normal syngeneic C3H mice but grow progressively in animals immunosuppressed by irradiation with ultraviolet light or by x-irradiation and thymectomy. Immunization of normal mice with 1591-specific lymphoblasts that had been generated in mixed lymphocyte-tumor cell cultures caused a loss of resistance to 1591 tumor cells, but the animals remained resistant to 1316 tumor cells. In vitro, spleen cells from animals immunized with 1591-specific lymphoblasts did not generate cytolytic T cells to 1591 fibrosarcoma cells, but spleen cells from the same animals responded normally to 1316 fibrosarcoma cells. Furthermore, spleen cells from animals immunized with 1591-specific lymphoblasts contained idiotype-specific T cells that lysed 1591-specific lymphoblasts, whereas 1316-specific lymphoblasts were unaffected. Immunization of normal animals with nonresponding lymphocytes from the same mixed lymphocyte-tumor cell cultures as the 1591-specific lymphoblasts showed normal responses to both tumors in vivo and in vitro. These results suggest that changes in the balance of tumor-specific and anti-idiotypic T lymphocyte clones can influence the capability of an individual to respond effectively to tumor antigens and can determine whether a tumor grows or regresses.