The role of L3T4-positive T lymphocytes in the generation of anti-tumor immunity in the mouse.

The role of L3T4-positive lymphocytes in the generation of anti-tumor immunity against syngeneic murine plasmacytoma was investigated. The induction of in vitro primary and secondary cytotoxic T lymphocytes against MOPC-104E plasmacytoma of BALB/c origin was completely inhibited by the addition of monoclonal anti-L3T4 antibody (GK1.5) during the culture period. The possible participation of L3T4-positive lymphocytes in the induction of cytotoxic T lymphocytes was confirmed by the pretreatment of non-immune or immune splenocytes with GK 1.5 plus complement followed by in vitro stimulation with the tumor. The treatment abrogated the ability to generate killer T cell activity. Because the effector killer T lymphocytes were not affected by GK1.5 plus complement treatment, the results strongly suggest that the L3T4-positive lymphocytes might be acting as helper cells for the generation of killer T lymphocytes. The in vivo effect of GK1.5 on anti-tumor immunity was then investigated. Tumor cell growth in mice which received GK1.5 injections was significantly accelerated and the mean survival time of the mice was shorter than that in control groups. On the other hand, mice with established anti-tumor immunity produced by hyperimmunization of tumor cells were affected differently from non-immune mice, showing 50% tumor incidence on day 30 after viable tumor challenge. The present study supports the contention that the L3T4-positive T lymphocytes, probably helper T cells, play a crucial role in the establishment of anti-tumor immunity.