Induction of Antitumor Cytotoxicity of Normal Syngeneic and Allogeneic Lymphocytes by Methotrexate

Summary

Nonimmune syngeneic and allogeneic mouse lymphocytes treated with 0.01 μg methotrexate (MTX) per ml destroyed L cells. The agglutination between lymphocytes and target cells was not intensified. MTX-treated lymphocytes added to allogeneic primary cultures of embryo cells produced a cytotoxic effect, but no effect was observed when they were added to syngeneic cells of primary embryo culture. Normal syngeneic lymphocytes treated with MTX suppressed tumor cell growth in mice in vivo. Treatment of lymphocytes with a 100 times higher dose of MTX failed to increase their cytotoxic effect in vitro and in vivo. The cytotoxicity of lymphocytes treated with MTX was eliminated by treatment with γ–irradiation (10,000 R), iodoacetate, and prednisolone. Simultaneous addition of MTX and citrovorum factor to the culture medium prevented the cytotoxic effect. Homogenates of lymphocytes treated with MTX were not cytotoxic.