Virus-specific production of IFN-gamma and IL-17 by CD4+ T cells from patients infected with West Nile virus (128.18)

Abstract The mechanisms that underlie the pathology of neuroinvasive West Nile virus (WNV) remain unknown. The goal of this study was to characterize the CD4+ T cell response to WNV in individuals with neuroinvasive and non-neuroinvasive symptoms. WNV-infected subjects were screened for CD4+ T cell reactivity with peptide pools derived from a library spanning the WNV polyprotein. Virus-specific CD4+ T cells were directed primarily against E, NS1, and NS3. Most WNV-specific CD4+ T cells produced IFN-γ. Surprisingly, IL-17 production was primarily associated with NS3-reactive cells. Single cell analysis revealed three distinct populations: IFN-γ+/IL-17-, IFN-γ+/IL-17+, IFN-γ-/IL-17+. Preliminary analysis suggests that elevated frequencies of virus-specific CD4+ T cells producing both IFN-γ and IL-17 are associated with protection against WNV neuroinvasive disease. This work was funded by a contract from NIAID (N01-AI-40066).