Interleukin-21 Receptor Expression on CD8 T Cells : A Potential Biomarker of HIV-1 Disease State and Trajectory

Summary Interleukin-21 (IL-21) is critical to CD8 T cell survival and potency during HIV-1 infection. Little is known about the signalling dynamics of IL-21 and its receptor (IL-21R) during this response. We examined the regulation of IL-21R on CD8 T cells from 53 HIV-1 infected, ART untreated individuals to determine the trends of IL-21R expression and regulation. We describe statistically significant associations between levels of increased IL-21R on CD8 T cells and expression of markers of exhaustion, excessive activation, and inability to inhibit viral replication in vivo. The same trends were observed at the cellular, extra-cellular and gene expression level. We also discovered that the IL-21R appeared to be down-regulated by its cytokine ligand IL-21 through receptor shedding that was inversely linked to CD8 T cell dysfunction markers. We suggest that IL-21R expression on CD8 T cells could be a novel predictive biomarker to inform monitoring of HIV-1 disease state and trajectory