Role of Gamma/Delta T Cells in West Nile Virus Pathogenesis

University Of Texas Med Br Galveston, Galveston TX

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): West Nile virus (WNV)-induced neurological disease has become an increasing public health concern in North America. Although immune responses to WNV have been the subject of intense investigation, the role of immune-mediated pathology in WNV-induced neurological diseases is incompletely understood. Our long- term goal is to understand the mechanism of WNV pathogenesis. In this proposal, we will focus on the role of one specific ?? T cell subtype- namely V?4+ T cells in WNV-induced encephalitis. We have previously shown that ?? T cells, the non-classical T cell population, are important for early control of WNV dissemination. In further investigation of the role of ?? T cell subsets in WNV infection, we have found that antibody depletion of V?1+ T cells enhances host susceptibility; while depletion of V??? + T cells reduces host susceptibility. Splenic V?1+ T cells expand dramatically at the early stage of WNV infection and produce significant amounts of IFN-?, data which lead us to suggest a role in protective immunity. In contrast, V?4+ T cells expand modestly in response to infection. Moreover, our data show that the aged mice are more susceptible to WNV infection than are young mice. Aged mice exhibit a slower and reduced response by V?1+ T cells, while maintaining a higher number of V??4+ T cells at the early stage of infection. Based on these facts, we hypothesize that V??4+ T cells are involved in the regulation of WNV pathogenesis. In Specific Aim1, we will further investigate the pathogenic effect of V??4+ T cells during WNV infection. In Specific Aim 2, we will attempt to understand the mechanisms by which V??4+ T cells regulate host immunity during WNV infection. WNV has now induced the largest outbreaks of viral encephalitis in North America and has become a public health concern. Results from this study will help to enhance our understanding of viral pathogenesis; they will also lead to the development of new strategies to prevent and treat WNV-induced encephalitis.