Quantitative and qualitative differences in CD4+ T cell responses for subjects with symptomatic and asymptomatic West Nile virus infection (P6125)

Abstract

Abstract The West Nile virus (WNV), a mosquito-borne flavivirus, induces a wide range of clinical manifestations in humans. While the majority of infections are essentially asymptomatic, a small percentage of inflections lead to neuroinvasive disease with symptoms ranging from mild disorientation to paralysis and death. Increased risk of symptomatic infection in immunosuppressed subjects could suggest that lack of effective immune responses against WNV may lead to worse outcomes. In this study, we utilized HLA class II tetramers to characterize the epitope specificity, frequency, and phenotype of WNV-specific T cells in subjects who had previously documented WNV infection. CD4+ T cell epitopes were present within all WNV fever proteins allowing broad characterization of WNV-specific responses. Ex vivo tetramer analysis revealed that WNV-specific CD4+ T cells were present at significantly higher frequencies in subjects with symptomatic infection than in those with no symptoms. CD4+ T cells had a memory phenotype in all WNV infected subjects, exhibited varying levels of activation, and produced multiple cytokines, including interferon-γ and IL-17. T cells from symptomatic subjects had a distinct phenotype, producing higher levels of Th2 cytokines after re-activation in vitro. Therefore, quantitative and qualitative differences in CD4+ T cell responses toward WNV are associated with neuroinvasive disease.