ABSTRACT
There are many evidences that dendritic cells (DC) can establish and maintain immunological tolerance through inducing the differentiation of regulatory T cells Treg. This study was purposed to explore the possibility to gene-rate Treg from bone marrow-derived DC (BM-DC) or spleen-derived DC (spDC) generated CD4(+) CD25(+) FOXP3(+) Treg by induction. Bone marrow immature DC (imDC) induced from bone marrow precursor cells of C57BL/6 mice by GM-CSF and IL-4; after culture for 6 day, imDC were stimulated by LPS for additional 16 hours and the mature DC (mDC) have been got; the spDC were collected from spleen of C57BL/6 mice by MACS. Co-culturing fresh BALB/c mouse CD4(+) T cells with these three sorts of DC above mentioned respectively was performed to generate CD4(+) CD25(+) FOXP3(+) Treg. The expression of FOXP3 in CD4(+) T cells was detected by flow cytometry, and the capacity of different DC generated CD4(+) CD25(+) FOXP3(+) Treg was evaluated. The results showed that stimulated by C57BL/6 immature or mature DC, the positive rate of FOXP3 in BALB/c CD4(+) T cells increased from (8.57 ± 1.14)% to (15.80 ± 1.35)%, (17.93 ± 1.45)% respectively (P < 0.01); while stimulated by spDC, the positive rate of FOXP3 in BALB/c CD4(+) T cells decreased from (8.57 ± 1.14)% to (3.95 ± 0.79)% (P < 0.05). It is concluded that the BM-DC but not spDC can generate Treg from CD4(+) T cells, BM-DC may mediate immune tolerance rather than the immune response.
Subject(s)
Animals , Female , Mice , Bone Marrow Cells , Cell Biology , Cell Differentiation , Cells, Cultured , Coculture Techniques , Dendritic Cells , Cell Biology , Forkhead Transcription Factors , Metabolism , Mice, Inbred BALB C , Mice, Inbred C57BL , Spleen , Cell Biology , T-Lymphocytes, Regulatory , Cell BiologyABSTRACT
<p><b>BACKGROUND</b>Although 32P-glass microspheres (32P-GMS) have been used in internal radiotherapy for malignant tumors, it has been one of the key obstacles to improve the effect of radiotherapy. We investigated the cellular and hypersensitive effect of combined use of low dose of cisplatin and interstitial injection of 32P-GMS on mouse solid tumor S180.</p><p><b>METHODS</b>The mice with solid tumor S180 were randomly divided into four groups (controls, cisplatin therapy, 32P-GMS therapy and combination therapy). The specimens of the mice were sectioned two weeks after treatment and weighed. The death rate of tumor cells and the inhibition rate of tumor were calculated respectively. The cell cycle and apoptosis rate were evaluated with flow-cytometry. The ultrastructural changes of the four groups were observed by a transmission electron microscope. The data were analyzed by the chi-square test.</p><p><b>RESULTS</b>The growth of tumor was slower in the combination therapy group than in the simple therapy groups by macrography. The inhibition rate and the death rate of tumor cells of the combination therapy group were significantly higher than those of the control group and the other two simple therapy groups (P < 0.05). More cell damages were displayed in the combination therapy group than in the other groups under the light and electronic microscope.</p><p><b>CONCLUSION</b>Low-dose cisplatin combined with interstitial injection of 32P glass microspheres could be used as an effective hypersensitive regimen for the internal radiotherapy of mouse solid tumor S180.</p>