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Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.

Feng E, Gao H, Su W, Yu C - Neural Regen Res (2012)

Bottom Line: Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone.The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Fuxing Hospital, Capital Medical University, Beijing 100038, China.

ABSTRACT
Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone. In this study, we established a novel vaccine procedure in rats, using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors. On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis. The survival rate of rats bearing C6 glioma was observed. Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma, and induced a strong cytolytic T lymphocyte response in rats. The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period. Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

No MeSH data available.


Related in: MedlinePlus

Peripheral changes in frequency of CD4+CD25+FOXP3+ regulatory T cells.Peripheral blood samples of each group (six rats per group) were stained for extracellular CD4, CD25 and intracellular FOXP3 expression. The plots shown were gated on CD4+ T cells.Percentages of double positive cells are indicated on the plots. Specific regions are marked, the gates and quadrants were set while analyzing the data based on isotype control antibody background staining.Representative scatter plots (A) and mean ± SD values of CD4+CD25+FOXP3+ regulatory T cells from five independent experiments carried out using six rats per group (B) are shown. Differences between the means of each group were tested using an unpaired t-test. aP < 0.05, bP < 0.01.
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Figure 6: Peripheral changes in frequency of CD4+CD25+FOXP3+ regulatory T cells.Peripheral blood samples of each group (six rats per group) were stained for extracellular CD4, CD25 and intracellular FOXP3 expression. The plots shown were gated on CD4+ T cells.Percentages of double positive cells are indicated on the plots. Specific regions are marked, the gates and quadrants were set while analyzing the data based on isotype control antibody background staining.Representative scatter plots (A) and mean ± SD values of CD4+CD25+FOXP3+ regulatory T cells from five independent experiments carried out using six rats per group (B) are shown. Differences between the means of each group were tested using an unpaired t-test. aP < 0.05, bP < 0.01.

Mentions: We measured the frequency of blood CD4+CD25+FOXP3+ Treg cells by fluorescent-activated cell sorting Calibur flow cytometry. The frequency of CD4+CD25+FOXP3+ Treg cells among CD4+ T cells was significantly higher in the PBS group than in healthy non-glioma rats (P = 0.001). There was no significant difference in Treg cell numbers between the T cells group and the PBS group (P = 0.47). The frequency of CD4+CD25+FOXP3+ Tregs was significantly lower in both the DCs group and DCs + T cells groups compared with the PBS group (P = 0.002, P = 0.001, respectively). In addition, there was a significantly lower frequency of CD4+CD25+FOXP3+ Tregs in the group receiving combination therapy compared with the group receiving C6 lysate-pulsed DCs alone (P = 0.04; Figure 6).


Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.

Feng E, Gao H, Su W, Yu C - Neural Regen Res (2012)

Peripheral changes in frequency of CD4+CD25+FOXP3+ regulatory T cells.Peripheral blood samples of each group (six rats per group) were stained for extracellular CD4, CD25 and intracellular FOXP3 expression. The plots shown were gated on CD4+ T cells.Percentages of double positive cells are indicated on the plots. Specific regions are marked, the gates and quadrants were set while analyzing the data based on isotype control antibody background staining.Representative scatter plots (A) and mean ± SD values of CD4+CD25+FOXP3+ regulatory T cells from five independent experiments carried out using six rats per group (B) are shown. Differences between the means of each group were tested using an unpaired t-test. aP < 0.05, bP < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308782&req=5

Figure 6: Peripheral changes in frequency of CD4+CD25+FOXP3+ regulatory T cells.Peripheral blood samples of each group (six rats per group) were stained for extracellular CD4, CD25 and intracellular FOXP3 expression. The plots shown were gated on CD4+ T cells.Percentages of double positive cells are indicated on the plots. Specific regions are marked, the gates and quadrants were set while analyzing the data based on isotype control antibody background staining.Representative scatter plots (A) and mean ± SD values of CD4+CD25+FOXP3+ regulatory T cells from five independent experiments carried out using six rats per group (B) are shown. Differences between the means of each group were tested using an unpaired t-test. aP < 0.05, bP < 0.01.
Mentions: We measured the frequency of blood CD4+CD25+FOXP3+ Treg cells by fluorescent-activated cell sorting Calibur flow cytometry. The frequency of CD4+CD25+FOXP3+ Treg cells among CD4+ T cells was significantly higher in the PBS group than in healthy non-glioma rats (P = 0.001). There was no significant difference in Treg cell numbers between the T cells group and the PBS group (P = 0.47). The frequency of CD4+CD25+FOXP3+ Tregs was significantly lower in both the DCs group and DCs + T cells groups compared with the PBS group (P = 0.002, P = 0.001, respectively). In addition, there was a significantly lower frequency of CD4+CD25+FOXP3+ Tregs in the group receiving combination therapy compared with the group receiving C6 lysate-pulsed DCs alone (P = 0.04; Figure 6).

Bottom Line: Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone.The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Fuxing Hospital, Capital Medical University, Beijing 100038, China.

ABSTRACT
Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone. In this study, we established a novel vaccine procedure in rats, using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors. On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis. The survival rate of rats bearing C6 glioma was observed. Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma, and induced a strong cytolytic T lymphocyte response in rats. The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period. Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

No MeSH data available.


Related in: MedlinePlus