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Genetic Mapping of Cytotoxicity of Dendritic Cells Against Tumor Cells Using C57BL/6 X DBA/2 (BXD) BXD Recombinant Inbred (RI) Strains of Mice
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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.
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