Intestinal intraepithelial lymphocytes exert potent protective cytotoxic activity during an acute virus infection

After systemic infection of mice with 10(4) PFU of lymphocytic choriomening itis virus (LCMV), infected cells are detected simultaneously in various or gans, including spleen and intestinal mucosa, Most notably, virus-infected cells are also present among CD11c(+) dendritic cells in the subepithelial area of the small intestinal mucosa, Some of these virus infected cells are in close spatial association with intestinal intraepithelial lymphocytes ( IEL), Therefore, we compared virus-specific cytotoxic activity of CD8 splen ocytes with that of IEL subsets. While ex vivo isolated TCR alpha beta(+)CD 8 alpha alpha(+) IEL exert only minimal virus specific cytotoxicity, maximu m specific killing mediated by TCR alpha beta(+)CD8 alpha beta(+) IEL on da y 8 postinfection exceeds maximum cytotoxic activity observed with CD8 sple nocytes when assessed in vitro. Maximum cytotoxic activity of IEL is preced ed by peak perforin and granzyme B mRNA expression in IEL, around day 6 pos tinfection, suggesting a recent activation in situ, The antivirus cytotoxic ity of in vivo primed IEL is further demonstrated by the protection from vi rus production in the spleen of mice infected with LCMV 10 h before adoptiv e cell transfer. These data indicate a potent priming of LCMV-specific IEL in situ after systemic LCMV infection and suggest that cytotoxic IEL marked ly contribute to the elimination of virus-infected cells in the intestinal mucosa.