Induction of Resident Memory CD8 + T cell Phenotypes to Eliminate the HIV reservoir

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Abstract
Enhancing effective antiviral responses within tissue compartments supporting HIV persistence at the time of antiretroviral therapy interruption will be necessary to limit viral rebound. With the hypothesis that CD8 + tissue resident memory T cell (T RM ) phenotypes might be more competent at controlling tissue viral recrudescence, we examined their capacity to control HIV after reactivation and the benefit of inducing T RM -like phenotypes through cytokine stimulation from blood. CD8 + T RM derived from cervical tissue were more efficient at eliminating reactivated HIV-infected CD4 + T cells compared to circulating effector CD8 + T cells. Expansion of CD8 + T RM -like phenotypes from blood through IL-15/TGF-β1 stimulation recovered functional HIV-specific CD8 + T cells displaying residency features, increased clonotypic diversity and mitochondrial function, and were the most efficient phenotypes at eliminating intact viruses after reactivation. Altogether, we provide a relevant therapeutic strategy to enhance elimination of persistent antigens like HIV by generating functional CD8 + T RM -like phenotypes.
Funding Information
  • Gilead Fellowship (GLD21-00049 and GLD23-00012)
  • MCIN/AEI/10.13039/501100011033 and the European Union «Next Generation EU»/PRTR (CNS2022-135549 and PID2023-149204OB-I00)
  • Fundació la Marató TV3 (201814 and 202112)

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