Loss of CD96 Expression as a Marker of HIV-Specific CD8+ T-Cell Differentiation and Dysfunction
oleh: Rémi Bunet, Rémi Bunet, Manon Nayrac, Hardik Ramani, Hardik Ramani, Mohamed Sylla, Madeleine Durand, Madeleine Durand, Carl Chartrand-Lefebvre, Jean-Pierre Routy, Alan L. Landay, Jean-Francois Gauchat, Nicolas Chomont, Nicolas Chomont, Petronela Ancuta, Petronela Ancuta, Daniel E. Kaufmann, Daniel E. Kaufmann, Nicole Bernard, Cécile L. Tremblay, Cécile L. Tremblay, Mohamed El-Far
| Format: | Article |
|---|---|
| Diterbitkan: | Frontiers Media S.A. 2021-05-01 |
Deskripsi
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.