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

摘要

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, CDS+ 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 mu M significantly suppressed mitogen-activated proliferation of peripheral blood mononuclear cells (p < 0.05). As2S2 at 10 PM inhibited production of IL-6, -10, -17A, tumor necrosis factor-alpha, and interferon-gamma from the activated peripheral blood mononuclear cells, though the effects were not statistically significant. As2S2 at 10 mu M 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. (C) 2015 Elsevier B.V. All rights reserved.