Strains of Shigella flexneri with different invasive and pathogenic potentials were inoculated into the intestinal lumen of acutely ligated loops in nonimmune rabbits. After 90 min, tissues processed for ultrastructural as well as light microscopy showed that the bacilli were phagocytosed by M cells over lymphoid follicles of Peyer's patches and carried in vacuoles into the epithelium. Nonpathogenic as well as pathogenic strains were readily taken up regardless of the presence of the 140-megadalton virulence plasmid. More virulent than avirulent shigellae were found in M cells at 90 min, reflecting replication or preferential uptake of the virulent strains. Heat-killed shigellae of the virulent strain were taken up by M cells to the same degree as the avirulent strains. Incubation of the bacteria for 18 h resulted in surface ulceration which was limited to epithelium overlying lymphoid follicles (M cell areas) in acute loops exposed to the virulent shigellae. Villus epithelium adjacent to the ulcerated follicular domes was intact, although there was mucus depletion. In the present study, we found that pathogenic shigellae appear to replicate in the M cells, escape from the phagocytic vesicles, and thereby initiate the ulcerations in this experimental model of dysentery. While initial antigen processing in the gut for a mucosal immune response may require uptake of luminal microorganisms by M cells, this may pose a threat under some circumstances.

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Using monoclonal antibodies to T and B lymphocytes, to natural killer cells, and to HLA-DR antigen, we characterized the lymphocyte population within the epithelial and lamina propria regions in control intestine and colon, and in grossly involved and in grossly uninvolved intestine and colon of patients with active inflammatory bowel disease. There were significantly more intraepithelial T cells in control ileum than in control colon. In comparison to control, there was a heterogeneity of alterations in intraepithelial and lamina propria T lymphocyte subsets (T11+, T8+, T4+) in inflammatory bowel disease. B lymphocytes were not detected within the lamina propria, except when found in and adjacent to lymphoid aggregates. Leu 7+ cells were uncommon in the lamina propria of control ileum and colon and in diseased tissues. The majority of intraepithelial lymphocytes did not express HLA-DR. Epithelial cells of control colon did not express HLA-DR while epithelial cells of control ileal tissues and of diseased colonic and ileal specimens expressed HLA-DR antigen. Only small numbers of lamina propria T cells expressed HLA-DR in both control and disease tissues. There was intense expression of HLA-DR by monocytes and modest expression of HLA-DR by capillary and lymphatic endothelial cells. The induction of HLA-DR expression by diseased colonic epithelium and the observation that lymphatic endothelium expresses HLA-DR are new observations, and we established that Leu 7+ cells are present in very small numbers in both normal and diseased intestine and colon.