Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8+ T cells and efficiently reduces chronic retroviral loads.

ABSTRACT: Chronic infections with human viruses, such as HIV and HCV, or mouse viruses, such as LCMV or Friend Virus (FV), result in functional exhaustion of CD8(+) T cells. Two main mechanisms have been described that mediate this exhaustion: expression of inhibitory receptors on CD8(+) T cells and expansion of regulatory T cells (Tregs) that suppress CD8(+) T cell activity. Several studies show that blockage of one of these pathways results in reactivation of CD8(+) T cells and partial reduction in chronic viral loads. Using blocking antibodies against PD-1 ligand and Tim-3 and transgenic mice in which Tregs can be selectively ablated, we compared these two treatment strategies and combined them for the first time in a model of chronic retrovirus infection. Blocking inhibitory receptors was more e

SUBMITTER: Dietze KK 

PROVIDER: S-EPMC3855586 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature