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

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.880873

DOI=10.3389/fmicb.2022.880873

ISSN=1664-302X

ABSTRACT=Background Despite the benefits of antiretroviral therapy (ART) for people with human immunodeficiency virus (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 was 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. TCF 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 was 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 TCF in regulation of T cell dysfunction.