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

Autor: Yanli He, Zhongping Liu, Shiang Huang, Xiaoqing Li, Jingming Yu, Junxia Yao, Jine Zheng, Jing Yang, Xingbing Wang, Jun Liu
Rok vydání: 2005
Předmět:
Zdroj: European Journal of Haematology. 75:468-476
ISSN: 1600-0609
0902-4441
DOI: 10.1111/j.1600-0609.2005.00537.x
Popis: 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 h i g h T-reg in the immune impairment of patients with acute myeloid leukemia (AML). Experimental design: The frequencies and phenotypes of CD4 + CD25 h i g h T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4 + CD25 h i g h T cells, CD4 + CD25 h i g h , and CD4 + CD25 - T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4 + CD25 h i g h 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 h i g h 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 h i g h T cells in peripheral blood. These cells were CD45-RA(-), CD69(-), CD45-RO(+), CD95(+), and intercellular CTLA-4(+), and secreted low levels of TNF-a and IL-10, but no IL-2, IL-4, IL-5, and IFN-y. They inhibited the proliferation and cytokine production (IL-2, IFN-y) 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 h i g h T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. Conclusions: The frequency of CD4 + CD25 h i g h 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 h i g h T cells.
Databáze: OpenAIRE