Lymphocyte Migration to the Intestinal Mucosa and its Relation to Mucosal Defense

摘要

Lymphocyte recirculation is a key phenomenon in immunology. However, in vivo regulation of the homing phenomenon of lymphoid cells to the intestinal mucosa, and its pathophysiological role in intestinal inflammation, has not been clearly understood. In this chapter we summarize the dynamic process of lymphocyte-endothelium recognition in the lymphoid and nonlymphoid area of intestine under an intravital microscope using fluorescence-labeled lymphocytes and discuss how regulation of lymphocyte homing is disturbed or altered under inflammatory conditions. Microvessels of intestinal lamina propria efficiently attracted gut-derived T cells via the a4(beta)7/MAdCAM-l system, but under tumor necrosis factor-alpha-induced inflamed conditions vascular cell adhesion molecule (VCAM)-l was also significantly involved. Under physiological conditions there was little lymphocyte adherence to the colonic mucosa, but in inflamed colonic mucosa T-cell migration became significant, comparable to that in the small intestinal mucosa. The chemokine CCL25/TECK may play an important role in T-cell migration to uninflamed as well as inflamed small intestine, but not colon. In an animal model of chronic colitis enhanced upregulation of mucosal addressin cell adhesion molecule (MAdCAM)-l levels in the colonic mucosa was demonstrated, and administration of anti-MAdCAM-1 antibody significantly attenuated the colonic injury, suggesting this adhesion molecule as a useful target for inflammatory bowel diseases.