Changes in the rate of crypt epithelial cell proliferation and mucosal morphology induced by a T-cell-mediated response in human small intestine.

The rate of crypt epithelial cell proliferation and mucosal morphology have been studied in vitro in explants of fetal human small intestine in organ culture in which a cell-mediated immune response has been elicited by stimulating lamina propria T cells with pokeweed mitogen or monoclonal anti-CD3 antibodies. Twelve hours after the addition of anti-CD3 or pokeweed mitogen, most lamina propria T cells expressed CD25. By 18 and 24 h after the addition of anti-CD3, there were significantly more crypt cells in the cell cycle than in controls, although villus height and crypt depth are the same in both groups. After 3 days, by dissecting microscopy, the villi appeared shorter in cultures in which the T cells were stimulated than in control cultures, and the mucosal surface was obscured by a layer of extruded enterocytes. Villus atrophy was confirmed by direct measurement of Feulgen-stained, microdissected villi. Crypts were longer in T-cell-stimulated cultures, and the rate of crypt epithelial cell proliferation measured by metaphase arrest was increased 10-fold. By electron microscopy, the microvilli and cellular morphology of the surface enterocytes were normal in T-cell-stimulated cultures. These experiments clearly show that a profound immune-mediated crypt epithelial cell hyperplasia can occur in the absence of damage to surface enterocytes.