GITR activation ex vivo impairs CD8 T cell function in people with HIV on antiretroviral therapy.

ABSTRACT: Glucocorticoid-induced tumor necrosis factor related protein (GITR) is a co-stimulatory immune checkpoint molecule constitutively expressed on regulatory T cells (T_regs) and on activated T conventional cells (T_conv). In blood collected from PWH on suppressive ART, GITR expression was reduced in multiple activated CD4 and CD8 T cell subsets but was increased in Tregs. HIV specific CD8 T cells expressed higher levels of GITR and programmed cell death protein 1 (PD-1) compared to total CD8 T cells. Following stimulation with HIV peptides and GITR-ligand (L), we demonstrated a significant decrease in killing by HIV specific CD8 T cells and an increased exhausted profile. T cell receptor co-stimulation with GITR-L abrogated T_reg suppression and induced expansion

SUBMITTER: Gubser C 

PROVIDER: S-EPMC10660494 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature