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Effects of B7-H1 molecule blockade on tumor infiltrating dendritic cellmediated Tcell function
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Abstract:
Objective: To explore the expression of B71, B72 and B7H1 on tumorinfiltrating dendritic cells (TIDC) and on splenic dendritic cells (SDC) , and to investigate TIDCmediated and SDCmediated Tcell function after blocking B7H1 expression in these dendritic cells. Methods: The TIDCs and SDCs were isolated from tumorbearing mice using antimouse CD11c magnetic beads. The expression of B71, B72 and B7H1 on TIDC and SDC was analyzed using flow cytometer. T cells were cocultured with TIDCs or SDCs for the mixed lymphocyte reaction (MLR), and monoclonal antibodies to B7H1 or the isotype control antibodies were added to the MLR cultures. Tcell proliferation was assessed using XTT method and the secretion of IL10 was detected using ELISA. Results: B71 and B72 positive TIDCs were significantly less than SDCs (P<0.01). B7H1 was moderately expressed on both TIDCs and SDCs (P>0.05). Tcell proliferation stimulated by TIDCs was weaker than that stimulated by SDCs; T cells produced more IL10 after TIDCs stimulation than after SDCs stimulation（P<0.01）. After blocking B7H1 on DCs, TIDCs showed a stronger stimulating ability on T cell proliferation compared with control antibodies, while SDCs did not have significant effect on T cell proliferation and production of IL10. Conclusion: Blocking B7H1 on TIDCs can significantly enhance their ability to activate T cells, and may elimilate TIDCmediated tumor immunosuppression.
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Supported by the Scientific Research Foundation of Huashan Hospital Affiliated to Fudan University (No.145)
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