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Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland
After systemic infection of mice with 104 PFU of
lymphocytic choriomeningitis virus (LCMV), infected cells are detected
simultaneously in various organs, 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
splenocytes with that of IEL subsets. While ex vivo isolated
TCR
ß+CD8+ IEL exert only minimal
virus-specific cytotoxicity, maximum specific killing mediated by
TCRß+CD8ß+ IEL on day 8 postinfection
exceeds maximum cytotoxic activity observed with CD8 splenocytes when
assessed in vitro. Maximum cytotoxic activity of IEL is preceded by
peak perforin and granzyme B mRNA expression in IEL around day 6
postinfection, suggesting a recent activation in situ. The antivirus
cytotoxicity of in vivo primed IEL is further demonstrated by the
protection from virus production in the spleen of mice infected with
LCMV 10 h before adoptive cell transfer. These data indicate a
potent priming of LCMV-specific IEL in situ after systemic LCMV
infection and suggest that cytotoxic IEL markedly contribute to the
elimination of virus-infected cells in the intestinal
mucosa.
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