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T CELL-MEDIATED DAMAGE IN THE HUMAN COLON IN ORGAN CULTURE A NEW IN-VITRO MODEL OF COLITIS

Immune mechanisms may be important in the pathogenesis of colonic inflammation To test this hypothesis, an organ-culture model was used to study the effects of T cell activation in human colonic mucosa.Lamina propria T cells in expant cultures of human fetal colon (16-20 weeks gestation, n=10) were activated in-situ using poke-weed mitogen or anti-CD atibody, and compared with controls.After 3 days of culture, immunohistochemistry demonstrated a 2-4 fold increase in crypt epithelial cell proliferation in T cell stimulated explants compared with controls; this was associated with a decrease in crypt goblet cell numbers of up to 20 fold. After 5 days, the surface epithelium in stimulated explants appeared flttened with severe loss of goblet cells, and by day 7, severe mucosal damage was observed under both light and electron microscopy. A fall in crypt goblet cells without hyperplasia had occurred in control cultures by day 7; however, the epithelium remained intact, and the degree of mucous depletion, and the rate at which it occurred, were less than in stimulated explants. Goblet cell depletion, crypt hyperplasia, and epithelial damage are common histological findings in colonic inflammation (particularly ulcerative colitis) These experiments suggest that T cells may have an important role in the pathogenesis of colitis. The model provides a new system whereby the mechanisms of T cell-mediated damage in the human colon can be studied.