Loss of CD96 Expression as a Marker of HIV-Specific CD8+ T-Cell Differentiation and Dysfunction

Rémi Bunet; Manon Nayrac; Hardik Ramani; Mohamed Sylla; Madeleine Durand; Carl Chartrand-Lefebvre; Jean Pierre Routy; Alan L. Landay; Jean Francois Gauchat; Nicolas Chomont; Petronela Ancuta; Daniel E. Kaufmann; Nicole Bernard; Cécile L. Tremblay; Mohamed El-Far

doi:10.3389/fimmu.2021.673061

Loss of CD96 Expression as a Marker of HIV-Specific CD8⁺ T-Cell Differentiation and Dysfunction

Rémi Bunet, Manon Nayrac, Hardik Ramani, Mohamed Sylla, Madeleine Durand, Carl Chartrand-Lefebvre, Jean Pierre Routy, Alan L. Landay, Jean Francois Gauchat, Nicolas Chomont, Petronela Ancuta, Daniel E. Kaufmann, Nicole Bernard, Cécile L. Tremblay, Mohamed El-Far

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8⁺ T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8⁺ T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8⁺ T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8⁺ T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8⁺ T-cell senescence and dysfunction in PLWH.

Original language	English (US)
Article number	673061
Journal	Frontiers in immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.673061
State	Published - May 27 2021
Externally published	Yes

Keywords

CD96
HIV
people living with HIV (PLWH)
T-cell dysfunction, IL-32
T-cell senescence

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.3389/fimmu.2021.673061

Cite this

Bunet, R., Nayrac, M., Ramani, H., Sylla, M., Durand, M., Chartrand-Lefebvre, C., Routy, J. P., Landay, A. L., Gauchat, J. F., Chomont, N., Ancuta, P., Kaufmann, D. E., Bernard, N., Tremblay, C. L., & El-Far, M. (2021). Loss of CD96 Expression as a Marker of HIV-Specific CD8⁺ T-Cell Differentiation and Dysfunction. Frontiers in immunology, 12, Article 673061. https://doi.org/10.3389/fimmu.2021.673061

Bunet, R, Nayrac, M, Ramani, H, Sylla, M, Durand, M, Chartrand-Lefebvre, C, Routy, JP, Landay, AL, Gauchat, JF, Chomont, N, Ancuta, P, Kaufmann, DE, Bernard, N, Tremblay, CL & El-Far, M 2021, 'Loss of CD96 Expression as a Marker of HIV-Specific CD8⁺ T-Cell Differentiation and Dysfunction', Frontiers in immunology, vol. 12, 673061. https://doi.org/10.3389/fimmu.2021.673061

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abstract = "Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8+ T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8+ T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8+ T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8+ T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8+ T-cell senescence and dysfunction in PLWH.",

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AU - Ramani, Hardik

AU - Sylla, Mohamed

AU - Durand, Madeleine

AU - Chartrand-Lefebvre, Carl

AU - Routy, Jean Pierre

AU - Landay, Alan L.

AU - Gauchat, Jean Francois

AU - Chomont, Nicolas

AU - Ancuta, Petronela

AU - Kaufmann, Daniel E.

AU - Bernard, Nicole

AU - Tremblay, Cécile L.

AU - El-Far, Mohamed

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Y1 - 2021/5/27

N2 - Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8+ T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8+ T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8+ T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8+ T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8+ T-cell senescence and dysfunction in PLWH.

AB - Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8+ T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8+ T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8+ T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8+ T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8+ T-cell senescence and dysfunction in PLWH.

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