The persistent immune activation that is typical of HIV-1 and SIV infection results in exhaustion and dysfunction of T and B cells; in T cells, this is marked by increased expression and signaling through the inhibitory receptor programmed death–1 (PD-1). Targeting this exhaustion pathway could result in improved antiviral immune responses, but there have been concerns that it would also lead to increased inflammation and immunopathology. In this issue of the JCI, Dyavar Shetty et al. demonstrate that blocking PD-1 actually reduced proinflammatory responses and improved immunity in the gut of SIV-infected rhesus macaques, suggesting that this might have therapeutic potential to prevent opportunistic infections in HIV-infected patients.
Jacob D. Estes
Simplified model of intestinal immunopathology and restoration with anti–PD-1 antibody treatment in SIV infection.