Global gene expression profiling in interleukin-12-induced activation of CD8(+) cytotoxic T lymphocytes against mouse mammary Carcinoma

Abstract

Interleukin-12 (IL-12) is a critical cytokine representing the link between the cellular and humoral branches of host immune defense apparatus. IL-12-induced cytotoxic lymphocyte (CTL) development is a central mechanism in immune responses against intracellular infectious agents as well as malignant growth. However, the molecular basis of tumor-specific CTL responses mediated by IL-12 remains poorly defined. In this study, we addressed this issue in a comprehensive manner to probe into IL-12-induced anti-tumor responses by global gene expression profiling of mRNA expression in CD8(+) T cells in a transplantable syngeneic mouse mammary carcinoma model treated or not with recombinant IL-12. A strong tumor regression was induced by the IL-12 treatment. An introspection of differential gene expression at an early stage of the IL-12-initiated CTL activation reveals interesting genes and molecular pathways that may account for the marked tumor regression, and is likely to provide a rich source of potential targets for further research and development of effective therapeutic modalities.

Figure 1

TS/A tumor growth in syngeneic mice. TS/A cells were injected subcutaneously in the middle of the right flank of BALB/c mice with 0.1 ml of a single-cell suspension containing the indicated number of TS/A cells. Tumor growth was monitored every 3–4 days and size measured with a caliper. Each data point is comprised of 4–11 mice. Error bars represent standard deviation. *p < 0.05; †p < 0.01; p < 0.0001.