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International Immunology, Vol. 12, No. 5, 701-709, May 2000
© 2000 Japanese Society for Immunology

Differential IL-12 responsiveness of T cells but not of NK cells from tumor-bearing mice in IL-12-responsive versus -unresponsive tumor models

Masayuki Iwasaki, Wen-Gong Yu, Yasuhiro Uekusa, Chigusa Nakajima, Yi-Fu Yang, Ping Gao, Rishani Wijesuriya, Hiromi Fujiwara and Toshiyuki Hamaoka

Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan

Correspondence to: H. Fujiwara

While IL-12 administration induces tumor regression through stimulating T cells in tumor-bearing mice, this IL-12 effect is observed in some but not all tumor models. The present study aimed to compare IL-12 responsiveness of T cells from tumor-bearing mice in IL-12-responsive (CSA1M and OV-HM) and -unresponsive (Meth A) tumor models. Tumor regression in IL-12-responsive tumor models required the participation of T cells, but not of NK1.1+ cells. Because a NK1.1+ cell population was the major producer of IFN-{gamma}, comparable levels of IFN-{gamma} production were induced in IL-12-responsive and -unresponsive tumor-bearing mice. This indicates that the amount of IFN-{gamma} produced in tumor-bearing individuals does not correlate with the anti-tumor efficacy of IL-12. In contrast, IL-12 responsiveness of T cells differed between the responsive and unresponsive models: purified T cells from CSA1M/OV-HM-bearing or Meth A-bearing mice exhibited high or low IL-12 responsiveness respectively, when evaluated by the amounts of IFN-{gamma} produced in response to IL-12. T cells from CSA1M- or OV-HM-bearing but not from Meth A-bearing mice exhibited enhanced levels of mRNA for the IL-12 receptor (IL-12R). These results indicate that a fundamental difference exists in IL-12 responsiveness of T cells between IL-12-responsive and -unresponsive tumor models, and that such a difference is associated with the expression of IL-12R on T cells.

Keywords: IL-12, NK cells, tumor models

Transmitting editor: T. Saito


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