Direct activation of human CD8(+) cytotoxic T lymphocytes by interleukin-18

Direct activation of human cytotoxic T lymphocytes (CTL) by interleukin (IL )-18 was observed in a system in which CTL effective against autologous tum or cells were generated. Peripheral blood mononuclear cells (PBMC) from tum or-bearing patients, after removal of natural killer (NK) cells, were cultu red 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 th e 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 th e 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 aut ologous CTL in humans and may thereby contribute to adoptive immunotherapy for tumors.