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

• Published in: Frontiers in immunology Vol. 12; p. 673061
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 27.05.2021
• Subjects: CD96; HIV; Immunology; people living with HIV (PLWH); T-cell dysfunction, IL-32; T-cell senescence
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.673061

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.