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Increased population of CD4 + CD25 high regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

2005; Wiley; Volume: 75; Issue: 6 Linguagem: Inglês

10.1111/j.1600-0609.2005.00537.x

1600-0609

Xingbing Wang, Jine Zheng, Jun Liu, Junxia Yao, Yanli He, Xiaoqing Li, J. Yu, Jing Yang, Zhongping Liu, Shiang Huang,

Immunotherapy and Immune Responses

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 + CD25 high T‐reg in the immune impairment of patients with acute myeloid leukemia (AML). Experimental design : The frequencies and phenotypes of CD4 + CD25 high T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4 + CD25 high T cells, CD4 + CD25 high , and CD4 + CD25 − T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4 + CD25 high 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 + CD25 high 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 + CD25 high 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 + CD25 high T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. Conclusions : The frequency of CD4 + CD25 high T‐reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4 + CD25 high T cells.