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© Michaela Muller-Trutwin
HIV
Publication : The Journal of clinical investigation

Reprogramming dysfunctional CD8+ T cells to promote properties associated with natural HIV control.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of clinical investigation - 05 Apr 2022

Perdomo-Celis F, Passaes C, Monceaux V, Volant S, Boufassa F, de Truchis P, Marcou M, Bourdic K, Weiss L, Jung C, Bourgeois C, Goujard C, Meyer L, Müller-Trutwin M, Lambotte O, Sáez-Cirión A,

Link to Pubmed [PMID] – 35380989

Link to DOI – 10.1172/JCI157549e157549

J Clin Invest 2022 Apr; ():

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/TCF-1 and mTORC through GSK3 inhibition to reprogram HIV-specific CD8+ T cells from non-controllers promoted functional capacities associated with natural control of infection. Features of such reprogrammed cells included the enrichment in TCF-1+ less-differentiated subsets, superior response to antigen, enhanced survival, polyfunctionality, metabolic plasticity, less mTORC1-dependency, improved response to γ-chain cytokines and 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.

https://pubmed.ncbi.nlm.nih.gov/35380989