Interventions towards functional cure: detailed phenotyping of the HIV-specific polyfunctional CD8+ T cell responseof controllers for therapeutic vaccine design.

SCHEME: AFR PhD

CALL: 2015

DOMAIN: BM - Life Sciences, Biology and Medicine

FIRST NAME: Philipp

LAST NAME: Adams

INDUSTRY PARTNERSHIP / PPP: No

INDUSTRY / PPP PARTNER:

HOST INSTITUTION: LIH

KEYWORDS: HIVControllers, CD8+T cell polyfunctionality, Functional Cure, Dendritic cells based-immunotherapy, co-inhibitory receptors

START: 2015-10-01

END: 2019-09-30

WEBSITE: https://www.lih.lu

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.

This site uses cookies. By continuing to use this site, you agree to the use of cookies for analytics purposes. Find out more in our Privacy Statement