骨髓瘤骨病（MBD）是因多发性骨髓瘤（MM）细胞与破骨细胞（OC）相互作用的恶性循环而导致进行性骨质破坏，严重影响 MM 患者生存质量和预后。免疫系统和骨系统关系密切，新近研究发现参与免疫调节的树突状细胞（DC）在MM环境下易转分化OC，此外我们前期研究发现另一重要免疫细胞Vγ9Vδ2 T细胞具有抑制DC向OC转分化的作用。因此，深入研究MM环境下Vγ9Vδ2 T细胞调控DC转分化为OC的作用及机制具有重要意义。本研究项目拟考察MM患者外周血Vγ9Vδ2 T细胞与MBD的关系；采用体外细胞共培养系统分析其影响DC转分化为OC的作用；采用基因芯片研究MM微环境下其对DC 转分化为OC过程表达谱变化的影响，并分析关键基因的调控网络和信号通路；采用MBD动物模型进一步探讨Vγ9Vδ2 T细胞过继免疫对DC在MBD中作用的影响，以期为Vγ9Vδ2 T细胞用于MBD的细胞免疫治疗提供理论和实验依据。

Myeloma bone disease (MBD) is characterized by progressive bone destruction due to enhanced osteoclasts (OC) activity because of the vicious cycle of interaction between multiple myeloma (MM) cells and OC. There is a close relationship between the immune system and bone system. It has been found recently that dendritic cells (DC), which are responsible for immunoregulation, tend to transdifferentiate into OC in the myeloma microenvironment. Furthermore, our previous study found that Vγ9Vδ2 T cells, another vital group of immune cells, can suppress DC transdifferentiation into OC. Thus, it is very important to further study the role and mechanism of Vγ9Vδ2 T cells regulating DC transdifferentiation into OC in the myeloma microenvironment. In this study, we will investigate MM patients to explore the relationship between the peripheral blood Vγ9Vδ2 T cells and MBD. We will use an in vitro co-culture system to make out the effect of Vγ9Vδ2 T cells on the process of DC transdifferentiation into OC. We will use gene microarray to detect Vγ9Vδ2 T cells' potential influence on the change of gene expression profiling of DC while transdifferentiating into OC in the myeloma microenvironment and to analyze the gene regulatory network and signal pathway of key gene. And finally we will use MBD mice model to investigate the effect of adoptive transfer of Vγ9Vδ2 T cells on the role of DC in the MBD. This study will provide theoretical and experimental evidence for applying Vγ9Vδ2 T cells as cell immunotherapy for MBD.