Characterization of enteric functional changes evoked by in vivo anti-CD3 T cell activation

Specific in vivo T cell activation initiated by treatment with anti-CD3 ant ibodies leads to diarrhea and structural damage of the intestinal mucosa. I n this study, the effect of T cell-induced mucosal damage on jejunal epithe lial ion transport, muscle contractility, and neuronal ACh release was asse ssed in Ussing chambers, organ baths, and a specialized perfusion apparatus , respectively. Time-matched control mice received hamster serum containing irrelevant antibodies. Jejunal segments from anti-CD3-treated mice display ed a significantly elevated epithelial baseline short-circuit current (whic h indicates increased ion transport) and a concomitant reduction in respons iveness to prosecretory stimuli (nerve stimulation, carbachol, and forskoli n). Longitudinal smooth muscle displayed altered spontaneous contractile ac tivity, length-tension relationships, and carbachol-stimulated contraction in tissues excised from mice 20 and 40 h posttreatment. Anti-CD3 treatment did not affect stimulated ACh release from myenteric plexus neurons. We con clude that specific T cell activation via anti-CD3 antibody results in dram atic alterations in jejunal epithelial and smooth muscle function. Such T c ell-induced changes in intestinal function may contribute to the symptomato logy of T cell-mediated enteropathies, including graft-versus-host disease, celiac disease, and idiopathic inflammatory bowel disease.