Submitted Abstract
Objective: To determine whether viral suppressive capacity (VSC) of CD8+ T cells canbe boosted by stimulation with HIV-1 peptides and whether the ability to control HIV-1replication correlates with immunological (CD8+ T cell cytokine production andphenotype) and viral reservoir measures (total HIV-1 DNA and cell-associated RNA) inwell-treated HIV-infected chronic progressors.Design: We compared VSC of peripheral CD8+ T cells to their cytokine productionprofile in response to peptide stimulation, detailed phenotype (18-color flow-cytometry),reservoir size (total HIV-1 DNA), basal viral transcription (unspliced cell-associatedRNA) and inducible viral transcription (tat/rev induced limiting dilution assay) in 36HIV+ patients on cART and six healthy donors.Results: We found that the VSC of CD8+ T cells can be increased by a priorstimulation with a pool of conserved HIV-1 gag peptides in a significant proportion ofprogressor patients. We also found that VSC after peptide stimulation was correlatedwith higher expression of immune checkpoint markers on subsets of terminallydifferentiated effector memory (TEMRA) CD8+ T cells as well as with production ofPowered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationIFN-¿, TNF-a and IL-10. We did not find a correlation between VSC and viral reservoirmeasures.Conclusions: These results add to a small body of evidence that the capacity of CD8+T cells to suppress viral replication is increased after stimulation with HIV-1 peptides.Interestingly, this VSC was correlated with expression of immune checkpoint markers,which are generally considered to be markers of exhaustion. Our findings may guidefurther investigations into immune phenotypes correlated with viral suppression.