PA-MSHA vaccine enhances inhibitory effect of acute myeloid leukemia-derived dendritic cells on regulatory T cells
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Abstract:
Objective: To investigate the influence of PA-MSHA (Pseudomonas aeruginosa with mannose sensitive hemagglutination pili) vaccine on the inhibitory effect of dendritic cells derived from acute myeloid leukemia (AML-DCs) on regulatory T cells (Treg). Methods: AML-DCs were induced with rhGM-CSF and IL-4 and were divided into three groups: control group, PA-MSHA, and TNF-a groups. After 24 h, the morphological features of AML-DCs in different groups were observed; the phenotypes were detected by flow cytometry; and the effect of AML-DCs on T cell proliferation was measured by mixed lymphocyte reaction and MTT assay. CD4+T cells were collected by magnetic bead assay from healthy peripheral blood cells and were incubated with different AML-DCs to induce differentiation of Treg. Then IL-10 and TGF-β were detected in different Treg supernatants by ELISA; CD4 and CD25 expressions on different Treg were determined by flow cytometry; and Foxp3 mRNA expression was examined by RT-PCR. Results: AML-DCs in PA-MSHA and TNF-α groups showed typical dendritic morphology, increased expressions of CDla, CD80, CD83, CD86 and HLA-DR (P<005), and enhanced abilities to induce proliferation of T cells compared with those in the control group (P<0.05). In addition, the levels of IL-10 and TGF-β, the expressions of CD4 and CD25 on Treg, and the expression of Foxp3 mRNA in PA-MSHA and TNF-α groups were all significantly lower than those in the control group (P<0.05), and these indices had no differences between PA-MSHA and TNF-α groups. Conclusion: PA-MSHA vaccine can promote the maturation of AML-DC, inhibit the differentiation of Treg from CD4+T cells, and enhance the inhibitory effect of AML-DC on Treg of AML patients.
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Project supported by the Program of Science and Technology of Gansu Province (No. 0804NKCA115)