GSE111435 Combination Anti-PD-1 and Anti-retroviral Therapy Provides Therapeutic Benefit Against SIV

Contributors : Geetha H Mylvaganam ; Lynette S Chea ; Gregory K Tharp ; Sakeenah Hicks ; Vijayakumar Velu ; Smita Iyer ; Jacob D Estes ; Steven E Bosinger ; Gordon J Freeman ; Rafi Ahmed ; Rama R AmaraSeries Type : Expression profiling by high throughput sequencingOrganism : Macaca mulattaTherapeutic strategies that enhance anti-viral immunity and reduce the viral reservoir are critical to achieving durable remission of HIV. The co-inhibitory receptor programmed death-1 (PD-1) regulates CD8+ T cell dysfunction during chronic HIV and SIV infections 1-4. In addition, PD-1+ CD4+ T cells constitute a significant fraction of the HIV/SIV viral reservoir5-7. We previously demonstrated that in vivo blockade of PD-1 during chronic SIV infection improves the function of anti-viral CD8+ T cells and B cells 4,8. However, the immunological effects of PD-1 blockade during anti-retroviral therapy (ART) and the potential to destabilize the persistent HIV/SIV reservoir have not been studied. Here, we show that administration of anti-PD-1 antibody (PD-1 Ab) 10 days prior to initiation of ART rapidly enhanced anti-viral CD8+ T cell function and diminished interferon stimulated genes (ISGs) that resulted in markedly improved viral suppression in plasma and better Th17 cell reconstitution in the rectal mucosa following ART initiation. In addition, PD-1 blockade during suppressive ART resulted in transient increases in plasma viremia, induction of gene signatures associated with effector CD8+ ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Macaca mulatta Source Type: research