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.