Increased frequency of Tim-3+ T cells is associated with symptomatic WNV disease clinical outcome (P6085)

Abstract

Abstract After a five-year period of steady annual cases, the 2012 West Nile virus (WNV) season was marked by a 4-fold resurgence with 5387 diagnosed infections, 2734 neuroinvasive cases and 243 deaths. Currently, no treatment or approved human vaccine is available for WNV infection. Understanding factors contributing to anti-WNV immunity and protection is therefore mandated. The present study investigates the surface expression patterns of negative T cell regulatory molecules over the course of WNV infection in a cohort of 32 WNV+ blood donors enrolled in longitudinal follow-up after initial WNV RNA+ blood donation (index) in those with asymptomatic (n=24) or symptomatic (n=8) disease outcome. We observed increased frequencies of Tim-3+CD4+ T cells during acute WNV infection (<90 days post-index) compared to uninfected controls (GEE P<0.0001). WNV+ donors had elevated frequencies of Tim-3+PD-1+ events in CD4+ and CD8+ T cells (P<0.05). Frequencies of Tim-3+ events in CD4+ and CD8+ T cells were higher in symptomatic than in asymptomatic subjects in the acute phase of infection (P=0.0009 and 0.033 on day 14 post-index, respectively), and symptomatic subjects had higher frequencies of Tim-3+CD4+ T cells throughout infection (GEE P<0.005). Our study highlights key mechanisms of immune vulnerability and reveals that T cell negative regulation is linked to symptomatic WNV disease and may serve as a novel target for improving protective responses or dampening inflammation and symptoms.