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Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia.


ABSTRACT:

Background

Acute myeloid leukemia (AML) is a common hematopoietic malignancy that has a high relapse rate, and the number of regulatory T cells (Tregs) in AML patients is significantly increased. The aim of this study was to clarify the role of Tregs in the immune escape of acute myeloid leukemia.

Methods

The frequencies of Tregs and the expression of PD-1, CXCR4 and CXCR7 were examined by flow cytometry. The expression of CTLA-4 and GITR was tested by MFI. Chemotaxis assays were performed to evaluate Treg migration. The concentrations of SDF-1?, IFN-? and TNF-? were examined by ELISA. Coculture and crisscross coculture experiments were performed to examine Treg proliferation and apoptosis and the effect of regulatory B cells (Breg) conversion.

Results

The frequencies of Tregs in peripheral blood and bone marrow in AML patients were increased compared with those in healthy participants. AML Tregs had robust migration towards bone marrow due to increased expression of CXCR4. AML Treg-mediated immunosuppression of T cells was achieved through proliferation inhibition, apoptosis promotion and suppression of IFN-? production in CD4+CD25- T cells. AML Bregs induced the conversion of CD4+CD25-T cells to Tregs.

Conclusion

In AML patients, the Breg conversion effect and robust CXCR4-induced migration led to Treg enrichment in bone marrow. AML Tregs downregulated the function of CD4+CD25- T cells, contributing to immune escape.

SUBMITTER: Wan Y 

PROVIDER: S-EPMC7249438 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia.

Wan Yuling Y   Zhang Congxiao C   Xu Yingxi Y   Wang Min M   Rao Qing Q   Xing Haiyan H   Tian Zheng Z   Tang Kejing K   Mi Yingchang Y   Wang Ying Y   Wang Jianxiang J  

BMC cancer 20200526 1


<h4>Background</h4>Acute myeloid leukemia (AML) is a common hematopoietic malignancy that has a high relapse rate, and the number of regulatory T cells (Tregs) in AML patients is significantly increased. The aim of this study was to clarify the role of Tregs in the immune escape of acute myeloid leukemia.<h4>Methods</h4>The frequencies of Tregs and the expression of PD-1, CXCR4 and CXCR7 were examined by flow cytometry. The expression of CTLA-4 and GITR was tested by MFI. Chemotaxis assays were  ...[more]

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