Altered IL-12 Signaling Pathways Contribute to the Deficient IFN-γ Production by T Splenocytes from Tumor-bearing Mice

Abstract

IFN-γ is a crucial cytokine produced by T and NK cells. Previous work from our laboratory has reported that in T cells of BALB/c mice bearing the D1-DMBA-3 mammary tumor, IFN-γ production is down-regulated, due to decreased expression of IL-12 by macrophages of tumor bearers. IL-12 is the main inducer of IFN-γ production in T and NK cells. To exert its function, IL-12 interacts with its receptor (IL-12R), activating a JAK/STAT signaling pathway. Our investigation suggests that there is also a deficiency in the response to IL-12 by T cells from tumor hosts. The present work reports the results of RT-PCR experiments in the study of the IL-12R expression on T cells from normal and tumor bearers. Data showed a deficient expression of the IL-12Rβ2 chain on T cells from tumor hosts. Gene expression arrays on IL-12-activated T cells from normal and tumor bearers confirmed the RT-PCR results, and also showed decreased expression of IL-18Rα in tumor bearers' T cells. Arrays also showed down-regulated expression of JAK2, STAT 1, 3, 4 and IRF-1. Finally, increased expression of SOCS 1,3,4,5 and 7, as well of Protein inhibitor of activated STATs (Pias) 1 and y was also observed in tumor bearers' T cells.