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

• Published in: European journal of haematology 2005-12, Vol.75 (6), p.468-476
• Main Authors: Wang, Xingbing, Zheng, Jine, Liu, Jun, Yao, Junxia, He, Yanli, Li, Xiaoqing, Yu, Jingming, Yang, Jing, Liu, Zhongping, Huang, Shiang
• Format: Article
• Language: English
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.2005.00537.x

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 super(+)CD25 super(high) T-reg in the immune impairment of patients with acute myeloid leukemia (AML). Experimental design: The frequencies and phenotypes of CD4 super(+)CD25 super(high) T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4 super(+)CD25 super(high) T cells, CD4 super(+)CD25 super(high), and CD4 super(+)CD25 super(-) T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4 super(+)CD25 super(high) and CD4 super(+)CD25 super(-) T cells were characterized by proliferation assays and cytokine production assays. In addition, the frequency of apoptotic and proliferating cells in CD4 super(+)CD25 super(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 super(+)CD25 super(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- alpha and IL-10, but no IL-2, IL-4, IL-5, and IFN- gamma . They inhibited the proliferation and cytokine production (IL-2, IFN- gamma ) of CD4 super(+)CD25 super(-) T cells, but improved IL-10 production under the co-culture of both subsets with stimulation, thus behaving as T-reg. Notably, CD4 super(+)CD25 super(high) T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. Conclusions: The frequency of CD4 super(+)CD25 super(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 super(+)CD25 super(high) T cells.