International Immunology, Vol. 12, No. 6, 909-914,
June 2000
© 2000 Japanese Society for Immunology
Relative contribution of NK and NKT cells to the anti-metastatic activities of IL-12
1 Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
2 CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST), Chiyoda-ku, Tokyo 101-0062, Japan
3 Department of Pathogenic Biochemistry, Research Institute of Wakan-yaku, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
4 Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
5 Central Institute for Experimental Animals, (CIEA), Nogawa, Miyamae, Kawasaki 216–0001, Japan
Correspondence to: K. Takeda
Conventional T cells, NK cells and NKT cells have been implicated in the anti-tumor activities induced by IL-12. Here we show that IL-12-induced immune responses are partially impaired in T and NKT cell-deficient RAG-2–/– mice, and in NKT cell-deficient CD1–/– mice. In response to a small dose (<1000 U) of IL-12, RAG-2–/– and CD1–/– mice demonstrated reduced cytotoxicity, serum IFN-
elevation and anti-metastatic activities; in contrast, in response to a high dose (>2000U) of IL-12, the IL-12-induced immune responses of RAG-2–/– and CD1–/– mice were indistinguishable from wild-type mice. The defective responses to low-dose IL-12 of RAG-2–/– mice were corrected by adoptive transfer of NKT cells but not NK cells. These findings indicate that both NK and NKT cells contribute to the anti-metastatic responses induced by IL-12, and that NKT cells are mostly responsible for the low-dose activities of this cytokine.
Keywords: anti-metastatic activity, IL-12, NK cell, NKT cell
Transmitting editor: T. Hamaoka
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