Accumulation of IL-12-activated antitumor effector cells into lymph nodes of tumor-bearing mice.
Simultaneous administration of high dose of IL-12 into tumor-inoculated mice resulted in a marked reduction of tumor growth in parallel with the augmented generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma-producing Th cells. We found that these IL-12-activated antitumor effector cells preferentially accumulated in peripheral lymph nodes concomitantly with lymphadenopathy. However, IL-12 rather induced disappearance of antitumor effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing mice showed a marked IFN-gamma production in response to not only IL-2, IL-12, anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0 melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL-12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site. Thus, IL-12 appeared to have a capability of stimulating selective migration of antitumor cells into lymph nodes and tumor local sites.
Yahata
T
T
Department of Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Japan.
Watanabe
K
K
Ohta
A
A
Ohmi
Y
Y
Sato
N
N
Santa
K
K
Abe
N
N
Iwakabe
K
K
Kaneko
S
S
Suzuki
N
N
Habu
S
S
Yasuda
S
S
Nishimura
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008206:Lymphatic Diseases; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013163:Splenomegaly; D014407:Tumor Cells, Cultured
D018664:Interleukin-12; D007371:Interferon-gamma