1. Differential IL-12 responsiveness of T cells but not of NK cells from tumor-bearing mice in IL-12-responsive versus -unresponsive tumor models.
- Author
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Iwasaki M, Yu WG, Uekusa Y, Nakajima C, Yang YF, Gao P, Wijesuriya R, Fujiwara H, and Hamaoka T
- Subjects
- Animals, Antigens immunology, Antigens, Ly, Antigens, Surface, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes immunology, Enzyme-Linked Immunosorbent Assay, Female, Interferon-gamma analysis, Interferon-gamma blood, Interleukin-12 immunology, Killer Cells, Natural drug effects, Lectins, C-Type, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, NK Cell Lectin-Like Receptor Subfamily B, Neoplasms, Experimental immunology, Proteins immunology, RNA, Messenger analysis, Receptors, Interleukin analysis, Receptors, Interleukin genetics, Receptors, Interleukin-12, Spleen immunology, T-Lymphocytes drug effects, Time Factors, Tumor Cells, Cultured, Tumor Escape, Interleukin-12 therapeutic use, Killer Cells, Natural immunology, Neoplasms, Experimental drug therapy, T-Lymphocytes immunology
- Abstract
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.
- Published
- 2000
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