GITR triggering has limited impact on HIV-specific CD8 T-cell function but enhances HIV transcription reactivation from latently infected CD4 T-cells.

Glucocorticoid-Induced TNFR-related protein (GITR) is a costimulatory molecule involved in the proliferation and effector functions of CD8 + and CD4 + T-cells. Recently, it has gained attention as a novel target for HIV immunotherapy. However, reports on its expression in people living with HIV (PLWH), as well as functional studies of GITR ligands effects in the context of HIV remain scarce. Here, we performed a thorough immune characterization of GITR expression in PLWH following HIV peptide stimulation. We found a prevalence of an effector memory phenotype on HIV-specific GITR-expressing CD8 + T-cells that correlated with viral control. Costimulation with a hexameric GITR ligand (GITRL) showed a modest improvement on antiviral function. Characterization of CD4 T-cells revealed an association between GITR expression among regulatory T-cells and viral control, as well as the prevalence of a central and effector memory T-cell phenotype. Remarkably, GITRL costimulation enhanced viral transcription without increasing the reservoir size, positioning GITR as an interesting target for the development of novel latency reversal agents.