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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

(2019) AIDS. 33(3). p.387-398
Author
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Abstract
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.
Keywords
HIV, CD8 T-cells, immune checkpoint, viral suppression, cytotoxic T-cell phenotype, functional cure, HIV persistence, HIV reservoir, immune exhaustion, viral suppressive capacity, INHIBITION ASSAY, INFECTION, RESPONSES, RESERVOIR, EXHAUSTION, VIREMIA, LOAD, CURE, NEUTRALIZATION, INTERRUPTION

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MLA
Pannus, Pieter et al. “In-vitro Viral Suppressive Capacity Correlates with Immune Checkpoint Marker Expression on Peripheral CD8+ T Cells in Treated HIV-positive Patients.” AIDS 33.3 (2019): 387–398. Print.
APA
Pannus, P., Adams, P., Willems, E., Heyndrickx, L., Florence, E., Rutsaert, S., De Spiegelaere, W., et al. (2019). In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients. AIDS, 33(3), 387–398.
Chicago author-date
Pannus, Pieter, Philipp Adams, Elisabeth Willems, Leo Heyndrickx, Eric Florence, Sofie Rutsaert, Ward De Spiegelaere, Linos Vandekerckhove, Carole Seguin-Devaux, and Guido Vanham. 2019. “In-vitro Viral Suppressive Capacity Correlates with Immune Checkpoint Marker Expression on Peripheral CD8+ T Cells in Treated HIV-positive Patients.” Aids 33 (3): 387–398.
Chicago author-date (all authors)
Pannus, Pieter, Philipp Adams, Elisabeth Willems, Leo Heyndrickx, Eric Florence, Sofie Rutsaert, Ward De Spiegelaere, Linos Vandekerckhove, Carole Seguin-Devaux, and Guido Vanham. 2019. “In-vitro Viral Suppressive Capacity Correlates with Immune Checkpoint Marker Expression on Peripheral CD8+ T Cells in Treated HIV-positive Patients.” Aids 33 (3): 387–398.
Vancouver
1.
Pannus P, Adams P, Willems E, Heyndrickx L, Florence E, Rutsaert S, et al. In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients. AIDS. 2019;33(3):387–98.
IEEE
[1]
P. Pannus et al., “In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients,” AIDS, vol. 33, no. 3, pp. 387–398, 2019.
@article{8606373,
  abstract     = {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.},
  author       = {Pannus, Pieter and Adams, Philipp and Willems, Elisabeth and Heyndrickx, Leo and Florence, Eric and Rutsaert, Sofie and De Spiegelaere, Ward and Vandekerckhove, Linos and Seguin-Devaux, Carole and Vanham, Guido},
  issn         = {0269-9370},
  journal      = {AIDS},
  keywords     = {HIV,CD8 T-cells,immune checkpoint,viral suppression,cytotoxic T-cell phenotype,functional cure,HIV persistence,HIV reservoir,immune exhaustion,viral suppressive capacity,INHIBITION ASSAY,INFECTION,RESPONSES,RESERVOIR,EXHAUSTION,VIREMIA,LOAD,CURE,NEUTRALIZATION,INTERRUPTION},
  language     = {eng},
  number       = {3},
  pages        = {387--398},
  title        = {In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients},
  url          = {http://dx.doi.org/10.1097/qad.0000000000002068},
  volume       = {33},
  year         = {2019},
}

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