Effects of arsenic disulfide on proliferation, cytokine production, and frequencies of CD4+, CD8+, and regulatory T cells in mitogen-activated human peripheral blood mononuclear cells

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Abstract

Influence of arsenic disulfide (As2S2) on human immune cells has little been investigated. Effects of As2S2 on proliferation, cytokine production, and frequencies of CD4+ T, CD8+ T and CD4+CD25+Foxp3+ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells were examined. Anti-proliferative effects of As2S2 on peripheral blood mononuclear cells activated by T-cell mitogen were assessed by a colorimetric assay. Cytokine concentrations in the culture medium were measured with beads-array procedures followed by flow cytometry. CD4+ T cells, CD8+ T cells and CD4+CD25+Foxp3+ regulatory T cells were stained with fluorescence-labeled specific antibodies followed by flow cytometry analysis. As2S2 at 1–10 μM significantly suppressed mitogen-activated proliferation of peripheral blood mononuclear cells (p < 0.05). As2S2 at 10 μM inhibited production of IL-6, -10, -17A, tumor necrosis factor-α, and interferon-γ from the activated peripheral blood mononuclear cells, though the effects were not statistically significant. As2S2 at 10 μM significantly suppressed the frequencies of CD4+ T and CD8+ T cells (p < 0.05), whereas significantly enhanced the frequency of CD4+CD25+Foxp3+ regulatory T cells (p < 0.05). The data suggest that As2S2 attenuates T cell-mediated immunity by not only suppressing the proliferation of T cells and cytokine release but also increasing the frequency of regulatory T cells. T cell-mediated autoimmunity contributes to bone marrow failure in myelodysplastic syndrome (MDS), and thus the above As2S2 effects are beneficial for the treatment of MDS patients.

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