Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function

Hong-Jiao Cai; Jue Shi; Lin-Bo Yin; Jie-Fu Zheng; Ya-Jing Fu; Yong-Jun Jiang; Hong Shang; Zi-Ning Zhang

doi:10.3389/fmicb.2022.880873

Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function

Front Microbiol. 2022 Jul 6:13:880873. doi: 10.3389/fmicb.2022.880873. eCollection 2022.

Authors

Hong-Jiao Cai^{1

2

3}, Jue Shi^{1

3

4}, Lin-Bo Yin^{1

3}, Jie-Fu Zheng^{1

3}, Ya-Jing Fu^{1

3}, Yong-Jun Jiang^{1

3}, Hong Shang^{1

3}, Zi-Ning Zhang^{1

3}

Affiliations

¹ NHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.
² Department of Central Laboratory, Dalian Municipal Central Hospital, Dalian, China.
³ Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China.
⁴ Department of Laboratory Medicine, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, China.

Abstract

Background: Despite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism.

Methods: In this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed in vitro.

Results: TCF7 mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4⁺ and CD8⁺ T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells.

Conclusion: Downregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction.

Keywords: HIV infection; T-cell factor 1; metabolism; mitochondrial function; proliferative capacity.