ENTERIC REOVIRUS INFECTION AS A PROBE TO STUDY IMMUNOTOXICITY OF THE GASTROINTESTINAL-TRACT

The gastrointestinal (GI) tract contains a complex immune system that defends the host against a wide range of pathogens and toxins. The GI tract is also exposed to many environmental toxins that could adversel y affect intestinal immunity, and few systems to study immunotoxicity of the GI tract have been described. We demonstrate that intestinal re ovirus infection can be used as a system to assess the effects of toxi ns on intestinal and systemic immunity. Mice were given various doses of cyclophosphamide (CY) for 5 days at doses ranging from 100 to 500 m g/kg by the oral route or 200 mg/kg by the intraperitoneal route, On d ay 3 of dosing, mice were orally infected with reovirus serotype 1, st rain Lang. The effects of CY on viral clearance, intestinal and system ic immune responses, and distribution of intestinal lymphocytes were a ssessed. Mice treated with CY failed to clear the virus in a dose-depe ndent manner, and serum anti-reovirus antibody titers were suppressed. Virus-specific IgA in cultures of intestinal tissue from CY-treated m ice was significantly reduced compared to controls, although total IgA production was not affected. The virus-specific cytotoxic T-cell resp onse in spleen was also suppressed in CY-treated animals. Cyclophospha mide treatment reduced the number and percentage of B-cells in Peyer's patches. Reovirus infection did not increase cellularity of Peyer's p atches in CY-treated mice. Cyclophosphamide treatment also had little effect on the phenotype of intestinal intraepithelial lymphocytes. The se data demonstrate that intestinal reovirus infection is useful in st udying exposure of the GI tract to immunotoxic agents. (C) 1998 Societ y of Toxicology.