Direct Activation of Human CD8+Cytotoxic T Lymphocytes by Interleukin-18

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Abstract
Direct activation of human cytotoxic T lymphocytes (CTL) by interleukin (IL)‐18 was observed in a system in which CTL effective against autologous tumor cells were generated. Peripheral blood mononuclear cells (PBMC) from tumor‐bearing patients, after removal of natural killer (NK) cells, were cultured in a medium containing IL‐1, ‐2, ‐4, and ‐6, with or without IL‐18, and stimulated with autologous tumor cells. IL‐18 increased the activity of the CTL and the proportion of autologous CD8+ T cells present after 28 days in the induction culture. When purified CD8+ T cells were cultured in the presence of IL‐18 and IL‐2 for 7 days, the CTL showed enhanced cytotoxic activity against autologous tumor cells. Moreover, a purified CD8+ T cell population, which did not exhibit any apparent cytotoxic activity against autologous tumor cells, displayed cytotoxic activity after 7‐day incubation with IL‐18. These results suggest that IL‐18 may be useful to generate autologous CTL in humans and may thereby contribute to adoptive immunotherapy for tumors.