Wnt signaling plays crucial roles in regulation of a wide range of processes in different cell types including immune cells and, in particular, dendritic cells and T cells. Growing indications point out that Wnt pathway components modulate the both innate and adaptive immune responses through regulating DC functions. We investigated the effects of recombinant DKK-3 protein on the phenotype and biological functions of bone marrow-derived DCs (BM-DCs) as well as T cell polarization. The phenotype and the cytokine production of BM-derived DCs in the presence DKK-3 were analyzed using flow cytometry and ELISA, respectively. Also, capability of DCs to activate T cells was evaluated by CFSE-labeled splenocytes. Regulatory T cell induction, T cell polarization, and cytokine secretion were assessed by flow cytometry and ELISA in splenocytes cultured in the presence of DKK-3. Our results showed that the expression of CD86 and CD40 increased in the DKK-3-treated DC, while the expression of PDL-1 and PDL-2 diminished. Furthermore, the presence of DKK-3 decreased IL-10 and IL-4 production and increased IFN-gamma production by treated DCs.DKK-3. Moreover, DKK-3 shifted naive CD4 T cells towards TH1 cells through up-regulation of T-bet and down-regulation of GATA-3. Our results, therefore, suggest that DKK-3 protein has the ability to promote the generation of Th1-immunostimulatory DCs from its precursors.
Using cellular adjuvants including dendritic cells (DCs) has provided a promising approach in immunotherapy of cancer. Our previous study showed that mice immunization with tumor cell lysate-pulsed DCs (TL-CD8α+DCs) could significantly suppress the tumor growth and increase mice survival. The aim of the present study was to investigate the impact of TL-CD8α+DC vaccine on intra-tumor and spleen lymphocyte subpopulations in tumor-bearing mice. A Balb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4 + , CD8+ and CD4T cells in mice immunized with TL-CD8α + DCs were studied. The cytotoxic activity of the lymphocytes and tumor growth inhibitory rate were also measured. Immunotherapy with TL-CD8α + DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4 + CD25 + Foxp3 + regulatory T cells as well as the tumor growth rate. There was also a decrease in the ratio of regulatory T cells to CD4 + and to CD8 + lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice. Immunization with TL-CD8α + DCs as well as CD8α + DCs significantly increased the splenocytes cytotoxic activity by 45.1% and 18.2% of control, respectively. In conclusion, the current study indicated that TL-CD8α + DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4 + and CD8 + lymphocytes and reducing regulatory T cells. This finding suggests the usefulness of TL-CD8α + DCs vaccine for cancer treatment.
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