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 adversely affect intestinal immunity, and few systems to study immunotoxicity of the GI tract have been described. We demonstrate that intestinal reovirus infection can be used as a system to assess the effects of toxins on intestinal and systemic immunity. Mice were given various doses of cyclophosphamide (CY) for 5 days at doses ranging from 100 to 500 mg/kg by the oral route or 200 mg/kg by the intraperitoneal route. On day 3 of dosing, mice were orally infected with reovirus serotype 1, strain Lang. The effects of CY on viral clearance, intestinal and systemic immune responses, and distribution of intestinal lymphocytes were assessed. Mice treated with CY failed to clear the virus in a dose-dependent manner, and serum anti-reovirus antibody titers were suppressed. Virus-specific IgA in cultures of intestinal tissue from CY-treated mice was significantly reduced compared to controls, although total IgA production was not affected. The virus-specific cytotoxic T-cell response in spleen was also suppressed in CY-treated animals. Cyclophosphamide treatment reduced the number and percentage of B-cells in Peyer's patches. Reovirus infection did not increase cellularity of Peyer's patches in CY-treated mice. Cyclophosphamide treatment also had little effect on the phenotype of intestinal intraepithelial lymphocytes. These data demonstrate that intestinal reovirus infection is useful in studying exposure of the GI tract to immunotoxic agents.