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 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.
Kohyama
M
M
RIKEN Cell Bank, Institute of Physical and Chemical Research [RIKEN], Ibaraki.
Saijyo
K
K
Hayasida
M
M
Yasugi
T
T
Kurimoto
M
M
Ohno
T
T
D000230:Adenocarcinoma; D002292:Carcinoma, Renal Cell; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005909:Glioblastoma; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007680:Kidney Neoplasms; D008213:Lymphocyte Activation / Q000187:drug effects; D009369:Neoplasms / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013274:Stomach Neoplasms; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D020382:Interleukin-18; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4