Distribution of rotavirus antigen in intestinal lymphoid tissues: potential role in development of the mucosal immune response to rotavirus

Abstract

Groups of suckling BALB/c mice were inoculated with murine rotavirus (MRV) at 5 days of age and sequentially tested for the presence of MRV antigen (Ag) in intestinal villus epithelium (VE), Peyer's patch (PP), mesenteric lymph node (MLN), spleen, liver and lung, using indirect immunofluorescence techniques (IF). MRV Ag was first detected in VE 24 h after oral administration of the virus and remained in VE for as long as 10 days post-inoculation (pi). MRV Ag was observed in the epithelium overlying PP at 3-7 days pi and in subepithelial and interfollicular areas in the PP between 3 and 20 days pi. MRV Ag was also detected in MLN during the same period of time. Small numbers of MRV-Ag-containing cells were detected in the lamina propria (LP) of intestinal villi at 10 days pi. Most MRV-Ag-containing cells in PP and MLN were Ia-positive but negative for Lyt-1, Lyt-2 and MAC-1 cell surface markers. MRV-Ag-containing cells were negative for surface or cytoplasmic immunoglobulin. Intestinal antibody response to MRV indicated by the presence of MRV-specific IgA plasma cells in LP was first detectable 10 days pi. Highest density of MRV-specific plasma cells was observed in the duodenum, with a similar distribution to that of MRV-Ag-containing cells in PP. These observations suggest that MRV-Ag uptake is largely limited to the PP associated epithelium and the virus Ag is subsequently transported to the underlying lymphoid follicles and MLN. These findings suggest a close relationship between the availability of MRV Ag in the lymphoid follicles at different locations and the subsequent development of local antibody responses in different segments of small intestine.