Interleukin-12 augments the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes from tumor-infiltrating lymphocytes.
Human tumor-infiltrating lymphocytes (TIL) were obtained from breast cancer, renal cancer or neuroblastoma to investigate the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes (CTL). When TIL were cultured with interleukin (IL)-2 (100 U/ml), the growth of TIL peaked around 8-10 days after the initiation of culture. In contrast, the proliferation of TIL cultured with IL-2 plus IL-12 peaked around 4-5 days after culture and tumor cells rapidly disappeared from the culture. To determine the generation of autologous tumor-reactive CD8+ CTL, TIL-derived CD8+ T cells were separated by FACStar. Both IL-2-activated and IL-2 plus IL-12-activated TIL-CD8+ T cells showed the same level of lymphokine-activated killer activity against a variety of tumor cells. However, TIL-CD8+ T cells activated with IL-2 plus IL-12 revealed greatly augmented cytotoxicity against autologous tumor cells compared with that induced by IL-2 alone. The autologous tumor cell-killing activity of TIL-CD8+ CTL was significantly inhibited by the addition of F(ab)2 anti-CD3 monoclonal antibody, indicating that these CTL recognize autologous tumor antigen through T cell receptor. These results imply that IL-12 is a novel cytokine which facilitates the generation of autologous tumor-reactive CD8+ CTL from TIL.
Kuge
S
S
Department of Immunology, Tokai University School of Medicine, Isehara.
Watanabe
K
K
Makino
K
K
Tokuda
Y
Y
Mitomi
T
T
Kawamura
N
N
Habu
S
S
Nishimura
T
T
D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D018664:Interleukin-12