ABSTRACT Localized infections in peripheral tissues such as the lungs present special challenges to the immune system. Cytotoxic T lymphocytes (CTL) play an important role in protective immunity against influenza infection by killing infected cells before they can release new virus. Since epithelial cells are the primary site of virus amplification, these virus-specific CTL must reach the mucosal surface of the lung airways very quickly if they are to make a meaningful contribution to immunity. Relatively little is known about the mechanisms that control local T cell migration to mucosal tissues. We recently showed that influenza proteins were present in the draining lymph nodes (DLN) of the respiratory tract until at least two months following pulmonary influenza infection, where they continued to be presented to virus-specific T cells. Restricted migration by virus-specific CTL in the respiratory tract while these viral antigens were present indicated that prolonged antigen-driven inflammation in the DLN helped retain activated or partially-activated T cells near the site of infection. We discuss the characteristics of the virus-specific CD8 T cells that respond to late antigen presentation after influenza infection within the context of current knowledge regarding T cell activation in lymphoid tissues and their potential contribution to protective immunity.
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