Interleukin-15 Role In The Anti-tumor Immune Mechanisms

In this study, we aimed at further investigating the role of interleukin-15 in antitumor response. It was designed to further evaluate the variations of the expression of MHC class I molecules, the sensitivity to NK cells and γδ t cells and tumorgenicity of the tumor cells after the endogenous expression of IL-15 was blocked.The project consists of three parts as following. First, we observed the effects of extogenous IL-15 on Jurkat cells which express IL-15 receptors. The results showed Jurkat cells can response to IL-15 in a dose-dependent manner, and the antibodies to IL-2 receptor β and y chains could block the IL-15-induced proliferation reaction and the antibody to IL-2 receptor β chain was more effective than that to IL-2 receptor y in blocking IL-15-trigging proliferation. Thus it was confirmed that IL-15 could promote the proliferation of some kind of tumor cells expressing IL-15 receptors.Secondly we obtained RD-10 cell line, which express low level of IL-15 through transfecting recombinant pcDNA3-anti-IL-15 into human rhabdomyosarcoma cell line RD by lipofectamine. After identified by Northern blot and Western blot, RD-10 and RD-neo cells (transfected the vector alone) were selected for further study.Thirdly, the expression of MHC class I molecules, function and tumorgenicity of RD, RD-neo and RD-10 cells were studied. The results of RT-PCR and flow cytometry showed the expression of MHC class I molecules on RD-10 cells were elevated. We also found RD-10 cells have higher level of RFX5 mRNA and protein expression than that of RD-neo cells. RFX5 is the most important subunit of RFX complex, this complex is of importance in transcription of MHC class I genes. From above, we preposed that IL-15 could down-regulate the expression of MHC class I through suppressing the expression of RFX5. The NK cytotoxicity was inhibited in RD-10 cells with high expression of MHC class I molecules, but the Y 5 T cells cytotoxicity was same among the three groups. Then the tumorgenicity of these tumor cells were determined in nude mice heterograft model in vivo.