Respiratory syncytial virus (RSV) is a significant respiratory pathogen that afflicts children and the elderly worldwide. The fact that individuals naturally infected with RSV are susceptible to re-infection insinuates that RSV has evolved a mechanism to modulate the host adaptive immune response. Our laboratory has previously demonstrated that following RSV challenge, a significant fraction of the virus-specific CD8+ T cells in the lungs exhibit impaired effector function (i.e. cytokine production and ex vivo cytolytic activity). This defective effector response is localized primarily to the CD8+ T cells accumulating in the lung compartment; is associated with a rapid decline in the frequency of peripheral CD8+ memory T cells; and is attributed to RSV infection. This proposal will address the mechanisms contributing to the immune dysregulation of CD8+ effector T cell activity by (1) assessing the molecular basis for the defect in effector function exhibited by virus-specific CD8+ T cells in the lung; and (2) identifying the RSV gene product that induces the partial inhibition of virus-specific CD8+ effector activity in the lung. The results from this study will provide a better understanding of the relationship between RSV and CD8+ T cell immunity. ? ?
