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In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients

Pannus, Pietera,b,c,*; Adams, Philippa,b,d,*; Willems, Elisabetha; Heyndrickx, Leoa; Florence, Erica; Rutsaert, Sofiec; De Spiegelaere, Warde; Vandekerckhove, Linosc; Seguin-Devaux, Caroled; Vanham, Guidoa,b

doi: 10.1097/QAD.0000000000002068
BASIC SCIENCE
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Objective: To determine whether viral suppressive capacity (VSC) of CD8+ T cells can be boosted by stimulation with HIV-1 peptides and whether the ability to control HIV-1 replication correlates with immunological (cytokine production and CD8+ T-cell phenotype) and viral reservoir measures (total HIV-1 DNA and cell-associated RNA) in well treated HIV-infected chronic progressors.

Design: We compared VSC of peripheral CD8+ T cells to cytokine production profile in response to peptide stimulation, detailed phenotype (17-color flow-cytometry), reservoir size (total HIV-1 DNA), basal viral transcription (unspliced cell-associated RNA) and inducible viral transcription (tat/rev induced limiting dilution assay) in 36 HIV+ patients on cART and six healthy donors.

Results: We found that the VSC of CD8+ T cells can be increased by prior stimulation with a pool of consensus HIV-1 gag peptides in a significant proportion of progressor patients. We also found that VSC after peptide stimulation was correlated with higher expression of immune checkpoint markers on subsets of terminally differentiated effector memory (TEMRA) CD8+ T cells as well as with production of IFN-γ, TNF-α and IL-10. We did not find a correlation between VSC and viral reservoir measures.

Conclusion: 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 guide further investigations into immune phenotypes correlated with viral suppression.

aDepartments of Biomedical and Clinical Sciences, Institute of Tropical Medicine, Antwerp

bDepartment of Biomedical Sciences, University of Antwerp

cDepartment of Internal Medicine, Ghent University, Ghent, Belgium

dDepartment of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg

eDepartment of Morphology, Ghent University, Ghent, Belgium.

Correspondence to Pieter Pannus, MSc, MPH, Departments of Biomedical and Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Nationalestraat 155, Belgium. Tel: +32 3 247 63 72; fax: +32 3 247 07 89; e-mail: ppannus@itg.be

Received 30 March, 2018

Accepted 13 July, 2018

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