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


METHODS
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-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(+)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.
Wang
Xingbing
X
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zheng
Jine
J
Liu
Jun
J
Yao
Junxia
J
He
Yanli
Y
Li
Xiaoqing
X
Yu
Jingming
J
Yang
Jing
J
Liu
Zhongping
Z
Huang
Shiang
S
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology*
D016207:Cytokines; D019394:Ki-67 Antigen; D015375:Receptors, Interleukin-2