Wang Xb

Increased population of CD4+CD25high regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

Abstract:  Purpose: Regulatory T cells (T‐reg) that control harmful autoimmune T cells in the periphery may also suppress the immune response against cancer. In this study we investigated the possible involvement of CD4+CD25high T‐reg in the immune impairment of patients with acute myeloid leukemia (AML). Experimental design: The frequencies and phenotypes of CD4+CD25high T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4+CD25high T cells, CD4+CD25high, and CD4+CD25− T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4+CD25high and CD4+CD25− T cells were characterized by proliferation assays and cytokine production assays. In addition, the frequency of apoptotic and proliferating cells in CD4+CD25high T cells were respectively evaluated by 7AAD and ki67 binding cells using flow cytometry. Results: Compared with healthy controls, AML patients had a higher proportion of CD4+CD25high T cells in peripheral blood. These cells were CD45‐RA(−), CD69(−), CD45‐RO(+), CD95(+), and intercellular CTLA‐4(+), and secreted low levels of TNF‐α and IL‐10, but no IL‐2, IL‐4, IL‐5, and IFN‐γ. They inhibited the proliferation and cytokine production (IL‐2, IFN‐γ) of CD4+CD25− T cells, but improved IL‐10 production under the co‐culture of both subsets with stimulation, thus behaving as T‐reg. Notably, CD4+CD25high T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. Conclusions: The frequency of CD4+CD25high T‐reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4+CD25high T cells.