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 journalArticlepeer-review

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 languageEnglish (US)
Article number673061
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - May 27 2021
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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