Abstract
T-cells in explants of human foetal small intestine (17-22 wk old) in organ culture were activated in situ with a T-cell mitogen (PWM) or monoclonal anti-CD3(T-cell)-antibody to directly test the hypothesis that activated T-cells play a role in the development of enteropathy in human small intestine. On days 1,3 and 5 post-activation, crypt cell production rate was measured by colchicine induced metaphase arrest, and villous height and crypt depth were directly measured after microdissection. T-cell activation in intestinal explants occured only in the lamina propria and was associated with crypt hypertrophy, short villi, and an increased rate of extrusion of enterccytes from the villous tips. The rate of crypt epithelial cell production was increased 10 - 20 fold compared with control cultures. These effects were not seen at day 1, peaked at day 3, and were still present at day 5. In younger fetal intestine which contains few T-cells, addition of PWM or anti-CD3-antibody only elicited minor changes in mucosal morphology. These experiments show that activated T-cells can cause changes in epithelial cell renewal in the human small intestine similar to those seen in a number of clinical enteropathies. This human model is easily manipulable in organ culture and should enable the dissection of the mechanisms underlying such changes.
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Cunha Ferreira, R., MacDonald, T. 1 CHANGES IN MUCOSAL MORPHOLOGY AND THE RATE OF CRYPT CELL RENEWAL INDUCED BY A CELL MEDIATED IMMUNE RESPONSE IN HUMAN SMALL INTESTINE. Pediatr Res 24, 405 (1988). https://doi.org/10.1203/00006450-198809000-00024
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DOI: https://doi.org/10.1203/00006450-198809000-00024