期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 132, 期 11, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI157549
关键词
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资金
- ANRS
- NIH [UM1AI164562]
- National Heart, Lung and Blood Institute (NHLBI)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Institute on Drug Abuse (NIDA)
- National Institute of Allergy and Infectious Diseases (NIAID)
- Pasteur-Roux-Cantarini fellowship from the Institut Pasteur
- Gilead
Virus-specific CD8(+) T cells play a central role in HIV-1 control and can be reprogrammed to enhance their antiviral potential through targeting specific signaling pathways.
Virus-specific CD8(+) T cells play a central role in HIV-1 natural controllers to maintain suppressed viremia in the absence of antiretroviral therapy. These cells display a memory program that confers them stemness properties, high survival, polyfunctionality, proliferative capacity, metabolic plasticity, and antiviral potential. The development and maintenance of such qualities by memory CD8(+) T cells appear crucial to achieving natural HIV-1 control. Here, we show that targeting the signaling pathways Wnt/transcription factor T cell factor 1 (Wnt/TCF-1) and mTORC through GSK3 inhibition to reprogram HIV-specific CD8(+) T cells from noncontrollers promoted functional capacities associated with natural control of infection. Features of such reprogrammed cells included enrichment in TCF-1(+) less-differentiated subsets, a superior response to antigen, enhanced survival, polyfunctionality, metabolic plasticity, less mTORC1 dependency, an improved response to gamma-chain cytokines, and a stronger HIV-suppressive capacity. Thus, such CD8(+) T cell reprogramming, combined with other available immunomodulators, might represent a promising strategy for adoptive cell therapy in the search for an HIV-1 cure.
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