[关键词]
[摘要]
目的:探讨DC的抗肿瘤免疫功能是否与其基因位点有关。方法:选择19株基因型明确的BXD纯系小鼠的树突状细胞(DC),MTT法和ELISA分析对DC吞噬肿瘤细胞的作用;肿瘤细胞诱导DC产生IL-12的能力;经肿瘤细胞刺激后的DC对T细胞增殖和IFN-γ分泌的影响进行测定。用流式细胞仪检测DC表面抗原标志CD80 和CD54。有关数据用MapManagerQTX and WebQTL软件对DC抗肿瘤免疫的基因位点进行分析。结果:DC刺激T细胞增殖的作用很大程度取决于BXD各系的遗传差异。DC吞噬肿瘤细胞及诱导IL-12产生的能力都与DC刺激T细胞的增殖相一致(P< 0.01)。基因位点定量分析(QTL)分析在第6和第13号染色体上有2个位点可能与DC的肿瘤抗原提呈加工功能和T细胞毒作用有关。结论:不同系的BXD小鼠,其DC的抗原提呈、加工能力不同。DC对肿瘤细胞生长的抑制与IL-12的诱导产生和DC表面共刺激分子的表达呈平行。其有关基因位点分别于第6和第13号染色体上。
[Key word]
[Abstract]
Objective:We utilized genotype well-defined 17 strains of BXD RI strains mice to determine if genetic loci underlie the dendritic cell response to the breast tumor cell line TS/A. Dendritic cells were assayed for tumor antigen processing, presenting function and IL-12 induction.Methods:T cells isolated from BXD strain 9 (BXD9, H-2d) or BXD strain 2 (H-2b) of mice previously immunized with breast tumor TS/A cells were stimulated in vitro with dendritic cells isolated from MHC matched BXD RI mice fed with TS/A tumor antigens for 3 days. Analysis of Dendritic phagocytosis apoptotic tumor cells.IL-12 induction of Dendritic cells isolated from BXD mice. Dendritic cells inhibit tumor cell growth and induce IFN-γ produced by T cells. Flow Cytometric Analysis of DC surface antigen expression. Dendritic cells Quantitative genetic mapping with MapManagerQTX and WebQTL. Results:Proliferation determined by MTT indicated that the ability of dendritic cells to stimulate T-cell proliferation greatly depended on BXD RI strain that was used as a stimulator. Furthermore, the phagocytosis capability of dendritic cells to tumor cells and induction of IL-12 in vitro were correlated (P<0.01) with the T-cell proliferative response stimulated by dendritic cells. Quantitative genetic mapping identified two loci that were associated with the processing of tumor antigens by dendrtic cells and the cytotoxicity response to the tumor cells.Conclusions:Processing and presenting of tumor Ag of Dendritic cells is variable and BXD strain dependent. Induction of the CD80 and CD54 Co-stimulation molecular is greatly affected by co-cultured tumor cells and BXD strain dependent. IL-12 induction and stimulation of tumor primed T cells are also BXD strain dependent. Inhibition of tumor growth by co-cultured DC were co-related with the induction of IL-12 and co-stimulation molecular induction and QTL mapped to Chromosome 6 and 13, respectively.
[中图分类号]
[基金项目]