AUTHOR=Bunet Rémi , Nayrac Manon , Ramani Hardik , Sylla Mohamed , Durand Madeleine , Chartrand-Lefebvre Carl , Routy Jean-Pierre , Landay Alan L. , Gauchat Jean-Francois , Chomont Nicolas , Ancuta Petronela , Kaufmann Daniel E. , Bernard Nicole , Tremblay Cécile L. , El-Far Mohamed TITLE=Loss of CD96 Expression as a Marker of HIV-Specific CD8+ T-Cell Differentiation and Dysfunction JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.673061 DOI=10.3389/fimmu.2021.673061 ISSN=1664-3224 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.